Search tips
Search criteria

Results 1-25 (452)

Clipboard (0)

Select a Filter Below

Year of Publication
1.  Repetitive Hyperbaric Oxygenation Attenuates Reactive Astrogliosis and Suppresses Expression of Inflammatory Mediators in the Rat Model of Brain Injury 
Mediators of Inflammation  2015;2015:498405.
The exact mechanisms by which treatment with hyperbaric oxygen (HBOT) exerts its beneficial effects on recovery after brain injury are still unrevealed. Therefore, in this study we investigated the influence of repetitive HBOT on the reactive astrogliosis and expression of mediators of inflammation after cortical stab injury (CSI). CSI was performed on male Wistar rats, divided into control, sham, and lesioned groups with appropriate HBO. The HBOT protocol was as follows: 10 minutes of slow compression, 2.5 atmospheres absolute (ATA) for 60 minutes, and 10 minutes of slow decompression, once a day for 10 consecutive days. Data obtained using real-time polymerase chain reaction, Western blot, and immunohistochemical and immunofluorescence analyses revealed that repetitive HBOT applied after the CSI attenuates reactive astrogliosis and glial scarring, and reduces expression of GFAP (glial fibrillary acidic protein), vimentin, and ICAM-1 (intercellular adhesion molecule-1) both at gene and tissue levels. In addition, HBOT prevents expression of CD40 and its ligand CD40L on microglia, neutrophils, cortical neurons, and reactive astrocytes. Accordingly, repetitive HBOT, by prevention of glial scarring and limiting of expression of inflammatory mediators, supports formation of more permissive environment for repair and regeneration.
PMCID: PMC4417949  PMID: 25972624
2.  Mediators of Gut Mucosal Immunity and Inflammation 
Mediators of Inflammation  2015;2015:765303.
PMCID: PMC4417598  PMID: 25969627
3.  Punicalagin Induces Nrf2/HO-1 Expression via Upregulation of PI3K/AKT Pathway and Inhibits LPS-Induced Oxidative Stress in RAW264.7 Macrophages 
Mediators of Inflammation  2015;2015:380218.
Reactive oxygen species (ROS) and oxidative stress are thought to play a central role in potentiating macrophage activation, causing excessive inflammation, tissue damage, and sepsis. Recently, we have shown that punicalagin (PUN) exhibits anti-inflammatory activity in LPS-stimulated macrophages. However, the potential antioxidant effects of PUN in macrophages remain unclear. Revealing these effects will help understand the mechanism underlying its ability to inhibit excessive macrophage activation. Hemeoxygenase-1 (HO-1) exhibits antioxidant activity in macrophages. Therefore, we hypothesized that HO-1 is a potential target of PUN and tried to reveal its antioxidant mechanism. Here, PUN treatment increased HO-1 expression together with its upstream mediator nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). However, specific inhibition of Nrf2 by brusatol (a specific Nrf2 inhibitor) dramatically blocked PUN-induced HO-1 expression. Previous research has demonstrated that the PI3K/Akt pathway plays a critical role in modulating Nrf2/HO-1 protein expression as an upstream signaling molecule. Here, LY294002, a specific PI3K/Akt inhibitor, suppressed PUN-induced HO-1 expression and led to ROS accumulation in macrophages. Furthermore, PUN inhibited LPS-induced oxidative stress in macrophages by reducing ROS and NO generation and increasing superoxide dismutase (SOD) 1 mRNA expression. These findings provide new perspectives for novel therapeutic approaches using antioxidant medicines and compounds against oxidative stress and excessive inflammatory diseases including tissue damage, sepsis, and endotoxemic shock.
PMCID: PMC4417599  PMID: 25969626
4.  Activins and Follistatin in Chronic Hepatitis C and Its Treatment with Pegylated-Interferon-α Based Therapy 
Mediators of Inflammation  2015;2015:287640.
Pegylated-interferon-α based therapy for the treatment of chronic hepatitis C (CHC) is considered suboptimal as not all patients respond to the treatment and it is associated with several side effects that could lead to dose reduction and/or termination of therapy. The currently used markers to monitor the response to treatment are based on viral kinetics and their performance in the prediction of treatment outcome is moderate and does not combine accuracy and their values have several limitations. Hence, the development of new sensitive and specific predictor markers could provide a useful tool for the clinicians and healthcare providers, especially in the new era of interferon-free therapy, for the classification of patients according to their response to the standard therapy and only subscribing the novel directly acting antiviral drugs to those who are anticipated not to respond to the conventional therapy and/or have absolute contraindications for its use. The importance of activins and follistatin in the regulation of immune system, liver biology, and pathology has recently emerged. This review appraises the up-to-date knowledge regarding the role of activins and follistatin in liver biology and immune system and their role in the pathophysiology of CHC.
PMCID: PMC4417604  PMID: 25969625
5.  Decreased IL-27 Negatively Correlated with Th17 Cells in Non-Small-Cell Lung Cancer Patients 
Mediators of Inflammation  2015;2015:802939.
The presence of Th17 cells and IL-27 is observed in a variety of inflammatory associated cancers. However, there are some data on the role of Th17 cells and IL-27 in the regulation of immune reactions in non-small-cell lung cancer (NSCLC). The aim of this study is to assess the variation of Th17 cells and IL-27 in the peripheral blood (PB) of patients with NSCLC. The proportion of Th17 cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometry. The serum concentrations of IL-27 and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of RORγt and IL-27 in the peripheral blood was examined by real-time quantitative polymerase chain reaction (QPCR). Expression of IL-27 was lower in NSCLC patients compared with normal controls. The frequency of Th17 cells was increased in NSCLC patients, accompanied by the upregulation of IL-17 and RORγt. IL-27 negatively correlated with the number of Th17 cells and the RORγt mRNA. Our results indicate that IL-27 might inhibit Th17 differentiation in NSCLC patients and better understanding of the regulatory effects of IL-27 on Th17 cells may shed light on potential new targets in cancer prevention and therapy.
PMCID: PMC4417605  PMID: 25969628
6.  In Memoriam of Iván Lásló Bonta (1922–2007) 
Mediators of Inflammation  2007;2007:38283.
PMCID: PMC1852885
7.  Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3,5-dione) Blocks the Chemotaxis of Neutrophils by Inhibiting Signal Transduction through IL-8 Receptors 
Mediators of Inflammation  2007;2007:10767.
We investigated the impact of curcumin on neutrophils. Chemotactic activity via human recombinant IL-8 (hrIL-8) was significantly inhibited by curcumin. Curcumin reduced calcium ion flow induced by internalization of the IL-8 receptor. We analyzed flow cytometry to evaluate the status of the IL-8 receptor after curcumin treatment. The change in the distribution of receptors intracellularly and on the cell surface suggested that curcumin may affect the receptor trafficking pathway intracellulary. Rab11 is a low molecular weight G protein associated with the CXCR recycling pathway. Following curcumin treatment, immunoprecipitation studies showed that the IL-8 receptor was associated with larger amounts of active Rab11 than that in control cells. These data suggest that curcumin induces the stacking of the Rab11 vesicle complex with CXCR1 and CXCR2 in the endocytic pathway. The mechanism for antiinflammatory response by curcumin may involve unique regulation of the Rab11 trafficking molecule in recycling of IL-8 receptors.
PMCID: PMC1940327  PMID: 17710245
8.  Maternal Plasma Procalcitonin Concentrations in Pregnancy Complicated by Preterm Premature Rupture of Membranes 
Mediators of Inflammation  2007;2007:35782.
Objectives. Our objective is to compare maternal plasma procalcitonin concentrations in preterm premature rupture of membranes (pPROM) and premature rupture of membranes (PROM) at term with their levels in uncomplicated pregnancy, and to determine whether these concentrations are useful in the diagnosis of pPROM cases suspected of infection and in the prediction of pPROM-to-delivery interval. Study design. Forty eight patients with pPROM, 30 with PROM at term, 31 healthy women at preterm gestation, and 33 healthy women at term were included. In pPROM group, analysis of procalcitonin concentrations with reference to leucocytosis, serum C-reactive protein, vaginal fluid culture, neonatal infection, histological chorioamnionitis and pPROM-to-delivery interval was carried out. Results. Procalcitonin concentrations in pPROM and PROM at term cases were comparable. However, in both groups procalcitonin values were significantly higher than in healthy controls in approximate gestational age. In pPROM group, procalcitonin concentrations between the patients with and without laboratory indices of infection were comparable, as well as between patients who gave birth to newborns with and without congenital infection, and between patients with and without histological chorioamnionitis. The predictive values of procalcitonin determinations were poor. Conclusion. The value of maternal plasma procalcitonin determinations in the diagnostics of pPROM cases suspected of intraamniotic infection, as well as for the prediction of pPROM-to-delivery interval, newborn's infection or histological chorioamnionitis is unsatisfactory. However, procalcitonin concentrations are elevated, both in patients with preterm and term PROMs in comparison to healthy pregnants, and therefore further evaluations are necessary to establish the role of procalcitonin in the pathophysiology of pregnancy.
PMCID: PMC1940053  PMID: 17710246
9.  Perinatal Changes of Cardiac Troponin-I in Normal and Intrauterine Growth-Restricted Pregnancies 
Mediators of Inflammation  2007;2007:53921.
Intrauterine growth restriction (IUGR) implies fetal hypoxia, resulting in blood flow redistribution and sparing of vital organs (brain, heart). Serum cardiac Troponin-I (cTnI), a well-established marker of myocardial ischaemia, was measured in 40 mothers prior to delivery, the doubly clamped umbilical cords (representing fetal state), and their 20 IUGR and 20 appropriate-forgestational-age (AGA) neonates on day 1 and 4 postpartum. At all time points, no differences in cTnI levels were observed between the AGA and IUGR groups. Strong positive correlations were documented between maternal and fetal/neonatal values (r ≥ .498, P ≤ .025 in all cases in the AGA and r ≥ .615, P ≤ .009 in all cases in the IUGR group). These results may indicate (a) normal heart function, due to heart sparing, in the IUGR group (b) potential crossing of the placental barrier by cTnI in both groups.
PMCID: PMC1939921  PMID: 17710247
10.  Characterization of the De Novo Biosynthetic Enzyme of Platelet Activating Factor, DDT-Insensitive Cholinephosphotransferase, of Human Mesangial Cells 
Mediators of Inflammation  2007;2007:27683.
Platelet activating factor (PAF), a potent inflammatory mediator, is implicated in several proinflammatory/inflammatory diseases such as glomerulonephritis, glomerulosclerosis, atherosclerosis, cancer, allergy, and diabetes. PAF can be produced by several renal cells under appropriate stimuli and it is thought to be implicated in renal diseases. The aim of this study is the characterization of DTT-insensitive cholinephosphotransferase (PAF-CPT) of human mesangial cell (HMC), the main regulatory enzyme of PAF de novo biosynthetic pathway. Microsomal fractions of mesangial cells were isolated and enzymatic activity and kinetic parameters were determined by TLC and in vitro biological test in rabbit washed platelets. The effect of bovine serum albumin (BSA), dithiothreitol (DTT), divalent cations (Mg2+ and Ca2+), EDTA, and various chemicals on the activity of PAF-CPT of HMC was also studied. Moreover, preliminary in vitro tests have been performed with several anti-inflammatory factors such as drugs (simvastatin, IFNa, rupatadine, tinzaparin, and salicylic acid) and bioactive compounds of Mediterranean diet (resveratrol and lipids of olive oil, olive pomace, sea bass “Dicentrarchus labrax,” and gilthead sea bream “Sparus aurata”). The results indicated that the above compounds can influence PAF-CPT activity of HMC.
PMCID: PMC1939920  PMID: 17710109
11.  Serum TNF-Alpha Level Predicts Nonproliferative Diabetic Retinopathy in Children 
Mediators of Inflammation  2007;2007:92196.
The aim of this study was identification of the immunologic markers of the damage to the eye apparatus at early stages of diabetes mellitus (DM) type 1 children. One hundred and eleven children with DM type 1 were divided into two groups: those with nonproliferative diabetic retinopathy (NPDR) and without retinopathy. All the children had their daily urine albumin excretion, HbA1c, C-peptide measured, 24-hour blood pressure monitoring, and ophthalmologic examination. Levels of TNF-α, IL-6, and IL-12 in serum were measured by ELISA tests (Quantikine High Sensitivity Human by R&D Systems, Minneapolis, Minn, USA). The NPDR children demonstrated a significantly longer duration of the disease in addition to higher HbA1c, albumin excretion rate, C-reactive protein, systolic blood pressure, as well as TNF-α and IL-6 levels than those without retinopathy. The logistic regression revealed that the risk of NPDR was strongly dependent on TNF-α [(OR 4.01; 95%CI 2.01−7.96)]. TNF-α appears to be the most significant predictor among the analyzed parameters of damage to the eye apparatus. The early introduction of the TNF-α antagonists to the treatment of young patients with DM type 1 who show high serum activity of the TNF-α may prevent them from development of diabetic retinopathy.
PMCID: PMC1906713  PMID: 17641733
12.  Pulmonary and Cardiorenal Cyclooxygenase-1 (COX-1), -2 (COX-2), and Microsomal Prostaglandin E Synthase-1 (mPGES-1) and -2 (mPGES-2) Expression in a Hypertension Model 
Mediators of Inflammation  2007;2007:85091.
Hypertensive mice that express the human renin and angiotensinogen genes are used as a model for human hypertension because they develop hypertension secondary to increased renin-angiotensin system activity. Our study investigated the cellular localization and distribution of COX-1, COX-2, mPGES-1, and mPGES-2 in organ tissues from a mouse model of human hypertension. Male (n = 15) and female (n = 15) double transgenic mice (h-Ang 204/1 h-Ren 9) were used in the study. Lung, kidney, and heart tissues were obtained from mice at necropsy and fixed in 10% neutral buffered formalin followed by embedding in paraffin wax. Cut sections were stained immunohistochemically with antibodies to COX-1, COX-2, mPGES-1, and mPGES-2 and analyzed by light microscopy. Renal expression of COX-1 was the highest in the distal convoluted tubules, cortical collecting ducts, and medullary collecting ducts; while proximal convoluted tubules lacked COX-1 expression. Bronchial and bronchiolar epithelial cells, alveolar macrophages, and cardiac vascular endothelial cells also had strong COX-1 expression, with other renal, pulmonary, or cardiac microanatomic locations having mild-to-moderate expression. mPGES-2 expression was strong in the bronchial and bronchiolar epithelial cells, mild to moderate in various renal microanatomic locations, and absent in cardiac tissues. COX-2 expression was strong in the proximal and distal convoluted tubules, alveolar macrophages, and bronchial and bronchiolar epithelial cells. Marked mPGES-1 was present only in bronchial and bronchiolar epithelial cells; while mild-to-moderate expression was present in other pulmonary, renal, or cardiac microanatomic locations. Expression of these molecules was similar between males and females. Our work suggests that in hypertensive mice, there are (a) significant microanatomic variations in the pulmonary, renal, and cardiac distribution and cellular localization of COX-1, COX-2, mPGES-1, and mPGES-2, and (b) no differences in expression between genders.
PMCID: PMC1906712  PMID: 17641732
13.  Proinflammatory Cytokine Gene Expression by Murine Macrophages in Response to Brugia malayi Wolbachia Surface Protein 
Mediators of Inflammation  2007;2007:84318.
Wolbachia, an endosymbiotic bacterium found in most species of filarial parasites, is thought to play a significant role in inducing innate inflammatory responses in lymphatic filariasis patients. However, the Wolbachia-derived molecules that are recognized by the innate immune system have not yet been identified. In this study, we exposed the murine macrophage cell line RAW 264.7 to a recombinant form of the major Wolbachia surface protein (rWSP) to determine if WSP is capable of innately inducing cytokine transcription. Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) mRNAs were all upregulated by the rWSP stimulation in a dose-dependant manner. TNF transcription peaked at 3 hours, whereas IL-1β and IL-6 transcription peaked at 6 hours post-rWSP exposure. The levels of innate cytokine expression induced by a high-dose (9.0 μg/mL) rWSP in the RAW 264.7 cells were comparable to the levels induced by 0.1 μg/mL E. coli-derived lipopolysaccharides. Pretreatment of the rWSP with proteinase-K drastically reduced IL-1β, IL-6, and TNF transcription. However, the proinflammatory response was not inhibited by polymyxin B treatment. These results strongly suggest that the major Wolbachia surface protein molecule WSP is an important inducer of innate immune responses during filarial infections.
PMCID: PMC1906711  PMID: 17641731
14.  Urinary Eosinophil Protein X in Children with Atopic Asthma 
Mediators of Inflammation  2007;2007:49240.
The aim of this study was to investigate the relationship between urinary eosinophil protein X (uEPX) and asthma symptoms, lung function, and other markers of eosinophilic airway inflammation in asthmatic school children. Methods. A cross-sectional study was performed in 180 steroid dependent atopic children with stable moderately severe asthma, who were stable on 200 or 500μg of fluticasone per day. uEPX was measured in a single sample of urine and was normalized for creatinine concentration (uEPX/c). Symptom scores were kept on a diary card. FEV1 and PD20 methacholine were measured. Sputum induction was performed in 49 and FENO levels measured in 24 children. Results. We found an inverse correlation between uEPX/c and FEV1 (r = −.20, P = .01) and a borderline significant correlation between uEPX/c and PD20 methacholine (r = −.15, P = .06). Symptom score, %eosinophils and ECP in induced sputum and FENO levels did not correlate with uEPX/c. Conclusion. uEPX/c levels did not correlate with established markers of asthma severity and eosinophilic airway inflammation in atopic asthmatic children.
PMCID: PMC1906710  PMID: 17641730
15.  Serum Interleukin-6 in Patients with Burning Mouth Syndrome and Relationship with Depression and Perceived Pain 
Mediators of Inflammation  2007;2007:45327.
Objective. To examine alteration of serum interleukin-6 and its clinical significance in burning mouth syndrome (BMS) patients. Methods. 48 BMS patients and 31 healthy controls participated in the study. Serum interleukin-6 was measured by means of ELISA. Hamilton rating scale of depression (HRSD) and visual analogue scale (VAS) were used to quantitiate depressive status and pain levels of subjects, respectively. Results. 15 (31%) patients displayed substantial depressive symptoms (HRSD ≧ 16). HRSD scores of patients were significantly higher than controls and positively correlated to their VAS values (P = .002). Serum interleukin-6 in patients was much lower than controls and negatively correlated to their VAS values (P = .011). However, no significant relations were found between interleukin-6 and HRSD scores (P = .317). Conclusions. Serum interleukin-6 in patients with burning mouth syndrome is decreased and negatively correlated to chronic pain. Both psychological and neuropathic disorders might act as precipitating factors in BMS etiopathogenesis.
PMCID: PMC1906709  PMID: 17641729
16.  Serum Leptin Levels in Patients with Ocular and Nonocular Behçet's Disease 
Mediators of Inflammation  2007;2007:31986.
Aims. To investigate serum leptin levels in Behçet's patients with or without ocular involvement compared with healthy subjects and the relationship between serum leptin and uveitis activity in patients with ocular involvement. Methods. Fifty-seven patients with Behçet's disease and 20 healthy control subjects were included in this study. While 27 patients had ocular involvement (18 had acute uveitis, 9 had inactive ocular involvement), 30 did not have ocular disease. C-reactive protein, alpha 1-antitrypsin, and serum leptin levels were measured in all samples. Results. There was a significant difference between the patients with Behçet's disease and control group for both logarithm of leptin (P = .000) and logarithm of CRP (P = .031). Logarithm of leptin in non-ocular Behçet's patients was significantly higher compared to its level in ocular Behçet's disease and controls (P = .009). There was a significant difference between the patients with active ocular disease and control group (P = .03). Conclusions. Leptin might have a possible role in the pathogenesis of Behçet's disease.
PMCID: PMC1906708  PMID: 17641728
17.  Plasma Interleukin-18 and Dendritic Cells in Males with Psoriasis Vulgaris 
Mediators of Inflammation  2007;2007:61254.
Peripheral blood dendritic cells seem to play a crucial role in psoriatic inflammatory processes. The aim of our study is to investigate the relationship between plasma interleukin-18 (IL-18) levels and blood dendritic cells in psoriatic patients. IL-18 plasma levels were measured by ELISA. Phenotypes of dendritic cell subsets were analyzed by double-colour flow cytometry. Plasma IL-18 level in psoriatic males was significantly higher, whereas counts of BDCA-2+ cells were lower than in the control group. The myeloid/plasmacytoid ratio was significantly higher in the patient group compared to the control one. In the patient group, significant negative correlations between plasma IL-18 level and both the BDCA-1+ and BDCA-2+ counts were found. BDCA-1+ counts correlated negatively with percentage of skin involvement. IL-18 seems to play a role in psoriasis pathogenesis. The decreased counts of blood plasmacytoid DCs in psoriatic patients might result from IL-18 down-regulation of plasmacytoid DC precursor proliferation.
PMCID: PMC1892645  PMID: 17611614
18.  Protective Role of Genistein in Acute Liver Damage Induced by Carbon Tetrachloride 
Mediators of Inflammation  2007;2007:36381.
Aim. In the present study, we investigated the protective effect of genistein in experimental acute liver damage induced by CCl4. Method. Forty rats were equally allocated to 5 groups. The first group was designated as the control group (group 1). The second group was injected with intraperitoneal CCl4 for 3 days (group 2). The third group was injected with subcutaneous 1 mg/kg genistein for 4 days starting one day before CCl4 injection. The fourth group was injected with intraperitoneal CCl4 for 7 days. The fifth group was injected with subcutaneous 1 mg/kg genistein for 8 days starting one day before CCl4 injection. Plasma and liver tissue malondialdehyde (MDA) and liver glutathione levels, as well as AST and ALT levels were studied. A histopathological examination was conducted. Results. Liver tissue MDA levels were found significantly lower in group 3, in comparison to group 2 (P < .05). Liver tissue MDA level in group 5 was significantly lower than that in group 4 (P < .001). Liver tissue glutathione levels were higher in group 5 and 3, relative to groups 4 and 2, respectively (P > .05 for each). Inflammation and focal necrosis decreased in group 3, in comparison to group 2 (P < .001 for each). Inflammation and focal necrosis in group 5 was lower than that in group 4 (P < .001). Actin expression decreased significantly in group 5, relative to group 4 (P < .05). Conclusion. Genistein has anti-inflammatory and antinecrotic effects on experimental liver damage caused by CCl4. Genistein reduces liver damage by preventing lipid peroxidation and strengthening antioxidant systems.
PMCID: PMC1892644  PMID: 17597837
19.  The Serum High-Sensitive C Reactive Protein and Homocysteine Levels to Evaluate the Prognosis of Acute Ischemic Stroke 
Mediators of Inflammation  2007;2007:15929.
Ischemic stroke is one of the most common causes of death worldwide and is most often caused by thrombotic processes. We investigated the changes in hsCRP and homocysteine levels, two of these risk factors, during the acute period of ischemic stroke and evaluated the relationship between these levels and the short-term prognosis. HsCRP and homocysteine levels were measured at the 2nd, 5th, and 10th days in forty patients admitted within second of an ischemic stroke. The clinical status of the patients was simultaneously evaluated with the Scandinavian stroke scale. The results were compared with 40 healthy control subjects whose age and sex were matched with the patients. The mean hsCRP levels of the patients were 9.4 ± 7.0 mg/L on the 2nd day, 11.0 ± 7.4 mg/L on the 5th day, and 9.2 ± 7.0 mg/L on the 10th day. The mean hsCRP level of the control subjects was 1.7 ± 2.9 mg/L. The mean hsCRP levels of the patients on the 2nd, 5th, and 10th days were significantly higher than the control subjects (P < .001). The patients' mean homocysteine levels were 40.6 ± 9.6 μmol/L on the 2nd day, 21.7 ± 11.1 μmol/L on the 5th day, and 20.7 ± 9.2 μmol/L on the 10th day. The mean homocysteine level of the control subjects was 11.2 ± 1.1 μmol/L. The homocysteine levels of the patients were higher than the control subjects at all times (P < .01). In conclusion, patients with stroke have a higher circulating serum hsCRP and homocysteine levels. Short-term unfavorable prognosis seems to be associated with elevated serum hsCRP levels in patients with stroke. Although serum homocysteine was found to be higher, homocysteine seems not related to prognosis.
PMCID: PMC1892643  PMID: 17597836
20.  Inhibitory Effect of Inflexinol on Nitric Oxide Generation and iNOS Expression via Inhibition of NF-κB Activation 
Mediators of Inflammation  2007;2007:93148.
Inflexinol, an ent-kaurane diterpenoid, was isolated from the leaves of Isodon excisus. Many diterpenoids isolated from the genus Isodon (Labiatae) have antitumor and antiinflammatory activities. We investigated the antiinflammatory effect of inflexinol in RAW 264.7 cells and astrocytes. As a result, we found that inflexinol (1, 5, 10 μM) suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells and astrocytes. Consistent with the inhibitory effect on iNOS and COX-2 expression, inflexinol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus. These results suggest that inflexinol inhibits iNOS and COX-2 expression through inhibition of NF-κB activation, thereby inhibits generation of inflammatory mediators in RAW 264.7 cells and astrocytes, and may be useful for treatment of inflammatory diseases.
PMCID: PMC1874678  PMID: 17541474
21.  Expression of Selected Integrins and Selectins in Bullous Pemphigoid 
Mediators of Inflammation  2007;2007:31051.
Blister development in bullous pemphigoid (BP) results from destruction of hemidesmosomes and basement membrane components within the dermoepidermal junction by autoantibodies. Adhesion molecules can take part in pathogenesis of this disease. The aim of the study was to determine the localization and expression of L- and E-selectins and β1, β3, and β4 integrins by immunohistochemistry in skin lesions of 21 patients with BP, compared with 10 healthy subjects. Expression of L and E selectins and β1, β3 integrins was detected mainly in basal keratinocytes and in inflammatory infiltrates in the dermis, expression of β4 integrin was irregular and was detected mainly in dermal part of the blister, while in the control group only weak and single expression of the examined molecules was detected in basal keratinocytes and endothelium cells. The obtained results reveal the important role of selected selectins and integrins in development of skin lesions in BP.
PMCID: PMC1868076  PMID: 17515951
22.  Resting Tension Affects eNOS Activity in a Calcium-Dependent Way in Airways 
Mediators of Inflammation  2007;2007:24174.
The alteration of resting tension (RT) from 0.5 g to 2.5 g increased significantly airway smooth muscle contractions induced by acetylcholine (ACh) in rabbit trachea. The decrease in extracellular calcium concentration [Ca2+]o from 2 mM to 0.2 mM reduced ACh-induced contractions only at 2.5 g RT with no effect at 0.5 g RT. The nonselective inhibitor of nitric oxide synthase (NOS), NG-nitro-L-arginine methyl ester (L-NAME) increased ACh-induced contractions at 2.5 g RT. The inhibitor of inducible NOS, S-methylsothiourea or neuronal NOS, 7-nitroindazole had no effect. At 2.5 g RT, the reduction of [Ca2+]o from 2 mM to 0.2 mM abolished the effect of L-NAME on ACh-induced contractions. The NO precursor L-arginine or the tyrosine kinase inhibitors erbstatin A and genistein had no effect on ACh-induced contractions obtained at 2.5 g RT. Our results suggest that in airways, RT affects ACh-induced contractions by modulating the activity of epithelial NOS in a calcium-dependent, tyrosine-phosphorylation-independent way.
PMCID: PMC1868075  PMID: 17515950
23.  Increased Endothelin-1 Levels of BAL Fluid in Patients with Behçet's Disease 
Mediators of Inflammation  2007;2007:93726.
Objective and background. Pulmonary aneurysms and thrombosis constitute a significant cause of morbidity and mortality in Behçet's disease (BD). Various factors have been studied to explore the pathogenesis of vascular involvement in BD. As endothelin (ET) is known for its potent vasoconstrictor and proinflammatory properties, we supposed that it is involved during the inflammatory process of BD pulmonary vasculitis. Methods. To investigate the role of ET in BD, ET-1 concentrations were measured in bronchoalveolar lavage fluid (BALF) of 18 nonsmoking BD patients with pulmonary manifestations and 12 control subjects. Immunoreactivity of ET-1 was also evaluated in alveolar macrophages (AMs) cytoplasm. Results. ET-1 levels in BD-BALF were significantly higher than those of controls. ET-1 levels were correlated with the number of alveolar macrophages, but not with BAL-CD4/CD8 ratio. ET-1-immunoreactivity was found mainly in AM of BD-BAL. Conclusions. Increased ET-1 production from AM is associated with pulmonary BD manifestations.
PMCID: PMC1852888  PMID: 17497041
24.  Calotropis procera Latex Extract Affords Protection against Inflammation and Oxidative Stress in Freund's Complete Adjuvant-Induced Monoarthritis in Rats 
Mediators of Inflammation  2007;2007:47523.
In view of the well-established anti-inflammatory properties of latex of Calotropis procera (DL), the present study was carried out to evaluate the protective effect of its methanol extract (MeDL) against inflammation and oxidative stress in monoarthritis induced by Freund's complete adjuvant (FCA) in rats. Intra-articular injection of FCA produced inflammation of the joint with a peak effect occurring on day 4 where a maximum increase in the levels of myeloperoxidase and inflammatory mediators like PGE2, TNF-α, and nitric oxide was observed. This was associated with oxidative stress with a marked reduction in the levels of glutathione, catalase, superoxide dismutase and glutathione peroxidase and an increase in the lipid peroxidation as indicated by the higher levels of thiobarbituric acid reactive substances (TBARSs). Subsequently on day 28 the histological analysis of the joint also revealed arthritic changes. Daily treatment of rats with MeDL (50 and 500 mg/kg) and standard anti-inflammatory drug rofecoxib (20 and 100 mg/kg), produced a significant attenuation in the inflammatory response and ameliorated the arthritic changes in the joint. The protection afforded by MeDL and rofecoxib was more pronounced than that of phenylbutazone and was associated with normalization of the levels of inflammatory mediators and biochemical parameters of oxidative stress. However, the overall protection afforded by rofecoxib was better than that of MeDL.
PMCID: PMC1852887  PMID: 17497032
25.  Insulin-Like Growth Factor (IGF)-I and Insulin in Normal and Growth-Restricted Mother/Infant Pairs 
Mediators of Inflammation  2007;2007:42646.
Insulin-like growth factor (IGF)-I and insulin are essential for fetal growth. We investigated perinatal changes of both factors in 40 mothers and their 20 appropriate-for-gestational-age (AGA) and 20 intrauterine-growth-restricted (IUGR) fetuses and neonates on day 1 (N1) and day 4 (N4) postpartum. Fetal and N1, but not N4, IGF-I levels were increased in AGA (P < .001 and P = .037, resp.). N1 insulin levels were lower in IUGR (P = .048). Maternal, fetal, and N1 IGF-I, and fetal insulin levels positively correlated with customized centiles (r = .374, P = .035, r = .608, P < .001, r = .485, P = .006, and r = .654, P = .021, resp.). Female infants presented elevated fetal and N4 IGF-I levels (P = .023 and P = .016, resp.). Positive correlations of maternal, fetal, and neonatal IGF-I levels, and fetal insulin levels with customized centiles underline implication of both hormones in fetal growth. IUGR infants present gradually increasing IGF-I levels. Higher IGF-I levels are documented in females.
PMCID: PMC1852886  PMID: 17497031

Results 1-25 (452)