Search tips
Search criteria

Results 1-18 (18)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
1.  Macrophage activation and polarization: nomenclature and experimental guidelines 
Immunity  2014;41(1):14-20.
Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors used in different ways. The lack of consensus on how to define macrophage activation in experiments in vitro and in vivo impedes progress in multiple ways, including the fact that many researchers still consider there to be only the two types of activated macrophages often termed M1 and M2. Here we describe a set of standards for the field encompassing three principles: the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation, with the goal of unifying experimental standards for diverse experimental scenarios. Collectively, we propose a common framework for macrophage activation nomenclature.
PMCID: PMC4123412  PMID: 25035950
2.  An unexpected twist to the activation of IKKβ: TAK1 primes IKKβ for activation by autophosphorylation 
Biochemical Journal  2014;461(Pt 3):531-537.
IKKβ {IκB [inhibitor of NF-κB (nuclear factor κB)] kinase β} is required to activate the transcription factor NF-κB, but how IKKβ itself is activated in vivo is still unclear. It was found to require phosphorylation by one or more ‘upstream’ protein kinases in some reports, but by autophosphorylation in others. In the present study, we resolve this contro-versy by demonstrating that the activation of IKKβ induced by IL-1 (interleukin-1) or TNF (tumour necrosis factor) in embryonic fibroblasts, or by ligands that activate Toll-like receptors in macrophages, requires two distinct phosphorylation events: first, the TAK1 [TGFβ (transforming growth factor β)-activated kinase-1]-catalysed phosphorylation of Ser177 and, secondly, the IKKβ-catalysed autophosphorylation of Ser181. The phosphorylation of Ser177 by TAK1 is a priming event required for the subsequent autophosphorylation of Ser181, which enables IKKβ to phosphorylate exogenous substrates. We also provide genetic evidence which indicates that the IL-1-stimulated, LUBAC (linear ubiquitin chain assembly complex)-catalysed formation of linear ubiquitin chains and their interaction with the NEMO (NF-κB essential modulator) component of the canonical IKK complex permits the TAK1-catalysed priming phosphorylation of IKKβ at Ser177 and IKKα at Ser176. These findings may be of general significance for the activation of other protein kinases.
We have discovered how a key enzyme that controls the immune system is switched on during infection by bacteria and viruses. Known by the acronym IKKβ, it triggers the production of many proteins that are needed to combat these pathogens.
PMCID: PMC4206954  PMID: 24911653
inhibitor of nuclear factor κB kinase (IKK); interleukin-1 (IL-1); linear ubiquitin chain assembly complex (LUBAC); nuclear factor κB (NF-κB); transforming growth factor β-activated kinase-1 (TAK1); BMDM, bone-marrow-derived macrophage; E, embryonic day; HA, haemaglutinnin; HEK, human embryonic kidney; HOIP, HOIL1 [haem-oxidized IRP2 (iron regulatory protein 2) ubiquitin ligase 1]-interacting protein; IκB, inhibitor of NF-κB; IKK, IκB kinase; IL-1, interleukin-1; JNK, c-Jun N-terminal kinase; LPS, lipopolysaccharide; LUBAC, linear ubiquitin chain assembly complex; MAPK, mitogen-activated protein kinase; M-CSF, macrophage colony-stimulating factor; MEF, mouse embryonic fibroblast; MKK, MAPK kinase; NEMO, NF-κB essential modulator; NF-κB, nuclear factor κB; PP1γ, protein phosphatase 1γ; TAB, TAK1-binding protein; TAK1, transforming growth factor β-activated kinase-1; TLR, Toll-like receptor; TNF, tumour necrosis factor; TRAF, TNF receptor-associated factor
3.  Bone Marrow-Specific Knock-In of a Non-Activatable Ikkα Kinase Mutant Influences Haematopoiesis but Not Atherosclerosis in Apoe-Deficient Mice 
PLoS ONE  2014;9(2):e87452.
The Ikkα kinase, a subunit of the NF-κB-activating IKK complex, has emerged as an important regulator of inflammatory gene expression. However, the role of Ikkα-mediated phosphorylation in haematopoiesis and atherogenesis remains unexplored. In this study, we investigated the effect of a bone marrow (BM)-specific activation-resistant Ikkα mutant knock-in on haematopoiesis and atherosclerosis in mice.
Methods and Results
Apolipoprotein E (Apoe)-deficient mice were transplanted with BM carrying an activation-resistant Ikkα gene (IkkαAA/AAApoe−/−) or with Ikkα+/+Apoe−/− BM as control and were fed a high-cholesterol diet for 8 or 13 weeks. Interestingly, haematopoietic profiling by flow cytometry revealed a significant decrease in B-cells, regulatory T-cells and effector memory T-cells in IkkαAA/AAApoe−/− BM-chimeras, whereas the naive T-cell population was increased. Surprisingly, no differences were observed in the size, stage or cellular composition of atherosclerotic lesions in the aorta and aortic root of IkkαAA/AAApoe−/− vs Ikkα+/+Apoe−/− BM-transplanted mice, as shown by histological and immunofluorescent stainings. Necrotic core sizes, apoptosis, and intracellular lipid deposits in aortic root lesions were unaltered. In vitro, BM-derived macrophages from IkkαAA/AAApoe−/− vs Ikkα+/+Apoe−/− mice did not show significant differences in the uptake of oxidized low-density lipoproteins (oxLDL), and, with the exception of Il-12, the secretion of inflammatory proteins in conditions of Tnf-α or oxLDL stimulation was not significantly altered. Furthermore, serum levels of inflammatory proteins as measured with a cytokine bead array were comparable.
Our data reveal an important and previously unrecognized role of haematopoietic Ikkα kinase activation in the homeostasis of B-cells and regulatory T-cells. However, transplantation of IkkαAA mutant BM did not affect atherosclerosis in Apoe−/− mice. This suggests that the diverse functions of Ikkα in haematopoietic cells may counterbalance each other or may not be strong enough to influence atherogenesis, and reveals that targeting haematopoietic Ikkα kinase activity alone does not represent a therapeutic approach.
PMCID: PMC3911989  PMID: 24498325
4.  Correction: Cigarette Smoke Induced Airway Inflammation Is Independent of NF-κB Signalling 
PLoS ONE  2013;8(10):10.1371/annotation/754d7b19-2dac-479b-a23c-db9fed0431be.
PMCID: PMC3806935
5.  Cigarette Smoke Induced Airway Inflammation Is Independent of NF-κB Signalling 
PLoS ONE  2013;8(1):e54128.
COPD is an inflammatory lung disease largely associated with exposure to cigarette smoke (CS). The mechanism by which CS leads to the pathogenesis of COPD is currently unclear; it is known however that many of the inflammatory mediators present in the COPD lung can be produced via the actions of the transcription factor Nuclear Factor-kappaB (NF-κB) and its upstream signalling kinase, Inhibitor of κB kinase-2 (IKK-2). Therefore the NF-κB/IKK-2 signalling pathway may represent a therapeutic target to attenuate the inflammation associated with COPD.
To use a range of assays, genetically modified animals and pharmacological tools to determine the role of NF-κB in CS-induced airway inflammation.
NF-κB pathway activation was measured in pre-clinical models of CS-induced airway inflammation and in human lung tissue from COPD patients. This data was complemented by employing mice missing a functional NF-κB pathway in specific cell types (epithelial and myeloid cells) and with systemic inhibitors of IKK-2.
We showed in an airway inflammation model known to be NF-κB-dependent that the NF-κB pathway activity assays and modulators were functional in the mouse lung. Then, using the same methods, we demonstrated that the NF-κB pathway appears not to play an important role in the inflammation observed after exposure to CS. Furthermore, assaying human lung tissue revealed that in the clinical samples there was also no increase in NF-κB pathway activation in the COPD lung, suggesting that our pre-clinical data is translational to human disease.
In this study we present compelling evidence that the IKK-2/NF-κB signalling pathway does not play a prominent role in the inflammatory response to CS exposure and that this pathway may not be important in COPD pathogenesis.
PMCID: PMC3551940  PMID: 23349803
6.  The Pore-Forming Toxin β hemolysin/cytolysin Triggers p38 MAPK-Dependent IL-10 Production in Macrophages and Inhibits Innate Immunity 
PLoS Pathogens  2012;8(7):e1002812.
Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections in human newborns and immune-compromised adults. The pore-forming toxin (PFT) β hemolysin/cytolysin (βh/c) is a major virulence factor for GBS, which is generally attributed to its cytolytic functions. Here we show βh/c has immunomodulatory properties on macrophages at sub-lytic concentrations. βh/c-mediated activation of p38 MAPK drives expression of the anti-inflammatory and immunosuppressive cytokine IL-10, and inhibits both IL-12 and NOS2 expression in GBS-infected macrophages, which are critical factors in host defense. Isogenic mutant bacteria lacking βh/c fail to activate p38-mediated IL-10 production in macrophages and promote increased IL-12 and NOS2 expression. Furthermore, targeted deletion of p38 in macrophages increases resistance to invasive GBS infection in mice, associated with impaired IL-10 induction and increased IL-12 production in vivo. These data suggest p38 MAPK activation by βh/c contributes to evasion of host defense through induction of IL-10 expression and inhibition of macrophage activation, a new mechanism of action for a PFT and a novel anti-inflammatory role for p38 in the pathogenesis of invasive bacterial infection. Our studies suggest p38 MAPK may represent a new therapeutic target to blunt virulence and improve clinical outcome of invasive GBS infection.
Author Summary
Our studies show β hemolysin/cytolysin (βh/c) from Group B Streptococcus (GBS), inhibits the activation of macrophages and the innate immune response to GBS. We show that βh/c triggers activation of mitogen activated protein kinase (MAPK) in GBS-infected macrophages leading to expression of the anti-inflammatory cytokine interleukin (IL)-10 and the suppression of genes required for effective anti-bacterial immunity. Furthermore, mice deficient in MAPK activation, specifically in macrophages, show increased resistance to invasive GBS infection. Our data describe a new role for a PFT in the evasion of host immunity that may have significant impact on the pathogenesis of invasive bacterial infections, and suggest targeting the signaling pathways triggered by PFTs in immune cells could increase innate immunity and host resistance.
PMCID: PMC3400567  PMID: 22829768
7.  The Nuclear Factor NF-κB Pathway in Inflammation 
The nuclear factor NF-κB pathway has long been considered a prototypical proinflammatory signaling pathway, largely based on the role of NF-κB in the expression of proinflammatory genes including cytokines, chemokines, and adhesion molecules. In this article, we describe how genetic evidence in mice has revealed complex roles for the NF-κB in inflammation that suggest both pro- and anti-inflammatory roles for this pathway. NF-κB has long been considered the “holy grail” as a target for new anti-inflammatory drugs; however, these recent studies suggest this pathway may prove a difficult target in the treatment of chronic disease. In this article, we discuss the role of NF-κB in inflammation in light of these recent studies.
Signals such as IL-1 and TNFα promote inflammation by up-regulating various target genes. Canonical and “alternative” NF-κB pathways have complex—sometimes opposing—roles in the process.
PMCID: PMC2882124  PMID: 20457564
8.  Regulation of macrophage function in tumors: the multifaceted role of NF-κB 
Blood  2009;113(14):3139-3146.
The pivotal role of tumor-associated macrophages (TAMs) in tumor progression is now well established. TAMs have been shown to influence multiple steps in tumor development including the growth, survival, invasion, and metastasis of tumor cells as well as angiogenesis and lymphangiogenesis in tumors. The molecular circuits that polarize TAMs toward such a protumoral phenotype are now the focus of intense investigation. The transcription factor, nuclear factor–κB (NF-κB), is a master regulator of many cellular processes and been shown to regulate various pathways that impact on the function of TAMs. Much evidence for this has come from the use of elegant transgenic murine tumor models in which modification of single components of the NF-κB signaling pathway has been shown to regulate the pro-tumor repertoire of TAMs. Here, we outline this evidence and attempt to reconcile the various views that have emerged recently over the exact role of NF-κB in this phenomenon.
PMCID: PMC2869029  PMID: 19171876
9.  The tumor-promoting actions of TNF-α involve TNFR1 and IL-17 in ovarian cancer in mice and humans 
The Journal of Clinical Investigation  2009;119(10):3011-3023.
Cytokines orchestrate the tumor-promoting interplay between malignant cells and the immune system. In many experimental and human cancers, the cytokine TNF-α is an important component of this interplay, but its effects are pleiotropic and therefore remain to be completely defined. Using a mouse model of ovarian cancer in which either TNF receptor 1 (TNFR1) signaling was manipulated in different leukocyte populations or TNF-α was neutralized by antibody treatment, we found that this inflammatory cytokine maintained TNFR1-dependent IL-17 production by CD4+ cells and that this led to myeloid cell recruitment into the tumor microenvironment and enhanced tumor growth. Consistent with this, in patients with advanced cancer, treatment with the TNF-α–specific antibody infliximab substantially reduced plasma IL-17 levels. Furthermore, expression of IL-1R and IL-23R was downregulated in CD4+CD25– cells isolated from ascites of ovarian cancer patients treated with infliximab. We have also shown that genes ascribed to the Th17 pathway map closely with the TNF-α signaling pathway in ovarian cancer biopsy samples, showing particularly high levels of expression of genes encoding IL-23, components of the NF-κB system, TGF-β1, and proteins involved in neutrophil activation. We conclude that chronic production of TNF-α in the tumor microenvironment increases myeloid cell recruitment in an IL-17–dependent manner that contributes to the tumor-promoting action of this proinflammatory cytokine.
PMCID: PMC2752076  PMID: 19741298
10.  p38α MAP kinase serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression 
Nature immunology  2008;9(9):1019-1027.
p38 mitogen-activated protein kinase (MAPK) mediates cellular responses to injurious stress and immune signaling. Among the multiple p38 isoforms, p38α is the most widely expressed in adult tissues and can be targeted by various pharmacological inhibitors. Here we investigated how p38α activation is linked to cell type-specific outputs using mouse models of cutaneous inflammation. We showed that both myeloid and epithelial p38α can signal to evoke inflammatory responses, yet the mode of skin irritation determines the cell type in which p38α serves the function. In addition, myeloid p38α induces self-limitation of acute inflammation via activation of MSK-dependent anti-inflammatory gene expression. These suggest a dual role of p38α in regulation of inflammation, and reveal a mixed potential for its inhibition as a therapeutic strategy.
PMCID: PMC2587092  PMID: 18677317
11.  An antiinflammatory role for IKKβ through the inhibition of “classical” macrophage activation 
The Journal of Experimental Medicine  2008;205(6):1269-1276.
The nuclear factor κB (NF-κB) pathway plays a central role in inflammation and immunity. In response to proinflammatory cytokines and pathogen-associated molecular patterns, NF-κB activation is controlled by IκB kinase (IKK)β. Using Cre/lox-mediated gene targeting of IKKβ, we have uncovered a tissue-specific role for IKKβ during infection with group B streptococcus. Although deletion of IKKβ in airway epithelial cells had the predicted effect of inhibiting inflammation and reducing innate immunity, deletion of IKKβ in the myeloid lineage unexpectedly conferred resistance to infection that was associated with increased expression of interleukin (IL)-12, inducible nitric oxide synthase (NOS2), and major histocompatibility complex (MHC) class II by macrophages. We also describe a previously unknown role for IKKβ in the inhibition of signal transducer and activator of transcription (Stat)1 signaling in macrophages, which is critical for IL-12, NOS2, and MHC class II expression. These studies suggest that IKKβ inhibits the “classically” activated or M1 macrophage phenotype during infection through negative cross talk with the Stat1 pathway. This may represent a mechanism to prevent the over-exuberant activation of macrophages during infection and contribute to the resolution of inflammation. This establishes a new role for IKKβ in the regulation of macrophage activation with important implications in chronic inflammatory disease, infection, and cancer.
PMCID: PMC2413025  PMID: 18490491
12.  “Re-educating” tumor-associated macrophages by targeting NF-κB 
The Journal of Experimental Medicine  2008;205(6):1261-1268.
The nuclear factor κB (NF-κB) signaling pathway is important in cancer-related inflammation and malignant progression. Here, we describe a new role for NF-κB in cancer in maintaining the immunosuppressive phenotype of tumor-associated macrophages (TAMs). We show that macrophages are polarized via interleukin (IL)-1R and MyD88 to an immunosuppressive “alternative” phenotype that requires IκB kinase β–mediated NF-κB activation. When NF-κB signaling is inhibited specifically in TAMs, they become cytotoxic to tumor cells and switch to a “classically” activated phenotype; IL-12high, major histocompatibility complex IIhigh, but IL-10low and arginase-1low. Targeting NF-κB signaling in TAMs also promotes regression of advanced tumors in vivo by induction of macrophage tumoricidal activity and activation of antitumor activity through IL-12–dependent NK cell recruitment. We provide a rationale for manipulating the phenotype of the abundant macrophage population already located within the tumor microenvironment; the potential to “re-educate” the tumor-promoting macrophage population may prove an effective and novel therapeutic approach for cancer that complements existing therapies.
PMCID: PMC2413024  PMID: 18490490
13.  Reduced Infiltration and Increased Apoptosis of Leukocytes at Sites of Inflammation by Systemic Administration of a Membrane-Permeable IκBα Repressor 
Arthritis and rheumatism  2004;50(8):2675-2684.
NF-κB activation is associated with several inflammatory disorders, including rheumatoid arthritis (RA), making this family of transcription factors a good target for the development of antiinflammatory treatments. Although inhibitors of the NF-κB pathway are currently available, their specificity has not been adequately determined. IκBα is a physiologic inhibitor of NF-κB and a potent repressor experimentally when expressed in a nondegradable form. We describe here a novel means for specifically regulating NF-κB activity in vivo by administering a chimeric molecule comprising the super-repressor IκBα (srIκBα) fused to the membrane-transducing domain of the human immunodeficiency virus Tat protein (Tat-srIκBα).
The Wistar rat carrageenan-induced pleurisy model was used to assess the effects of in vivo administration of Tat-srIκBα on leukocyte infiltration and on cytokine and chemokine production.
Systemic administration of Tat-srIκBα diminished infiltration of leukocytes into the site of inflammation. Analysis of the recruited inflammatory cells confirmed uptake of the inhibitor and reduction of the NF-κB activity. These cells exhibited elevated caspase activity, suggesting that NF-κB is required for the survival of leukocytes at sites of inflammation. Analysis of exudates, while showing decreases in the production of the proinflammatory cytokines tumor necrosis factor α and interleukin-1β, also revealed a significant increase in the production of the neutrophil chemoattractants cytokine-induced neutrophil chemoattractant 1 (CINC-1) and CINC-3 compared with controls. This result could reveal a previously unknown feedback mechanism in which infiltrating leukocytes may down-regulate local production of these chemokines.
These results provide new insights into the etiology of inflammation and establish a strategy for developing novel therapeutics by regulating the signaling activity of pathways known to function in RA.
PMCID: PMC2596347  PMID: 15334484
14.  Inflammation and Cancer: A Double-Edged Sword 
Cancer cell  2007;12(4):300-301.
Recent literature has highlighted an important role of inflammation in promoting cancer. However, the immune system can also play a central role in protecting the body against cancer as well as infection, although its role in cancer is not well understood. A study published in the September issue of Nature Medicine adds a new twist to the role of inflammation in cancer. Apetoh et al. describe how activation of innate immunity after conventional radiation or chemotherapy can trigger protective antitumor immunity.
PMCID: PMC2592547  PMID: 17936555
15.  Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection 
The World Health Organization estimates that lower respiratory tract infections (excluding tuberculosis) account for ∼35% of all deaths caused by infectious diseases. In many cases, the cause of death may be caused by multiple pathogens, e.g., the life-threatening bacterial pneumonia observed in patients infected with influenza virus. The ability to evolve more efficient immunity on each successive encounter with antigen is the hallmark of the adaptive immune response. However, in the absence of cross-reactive T and B cell epitopes, one lung infection can modify immunity and pathology to the next for extended periods of time. We now report for the first time that this phenomenon is mediated by a sustained desensitization of lung sentinel cells to Toll-like receptor (TLR) ligands; this is an effect that lasts for several months after resolution of influenza or respiratory syncytial virus infection and is associated with reduced chemokine production and NF-κB activation in alveolar macrophages. Although such desensitization may be beneficial in alleviating overall immunopathology, the reduced neutrophil recruitment correlates with heightened bacterial load during secondary respiratory infection. Our data therefore suggests that post-viral desensitization to TLR signals may be one possible contributor to the common secondary bacterial pneumonia associated with pandemic and seasonal influenza infection.
PMCID: PMC2271005  PMID: 18227219
16.  Novel biphasic role for lymphocytes revealed during resolving inflammation 
Blood  2008;111(8):4184-4192.
Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1−/− mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D2. However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), γ/δ T, CD4+/CD25+, and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1−/− and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox−/− mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection.
PMCID: PMC2602590  PMID: 18218853
17.  Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1 
The Journal of Experimental Medicine  2006;203(8):1883-1889.
Glucocorticoids (GCs), which are used in the treatment of immune-mediated inflammatory diseases, inhibit the expression of many inflammatory mediators. They can also induce the expression of dual specificity phosphatase 1 (DUSP1; otherwise known as mitogen-activated protein kinase [MAPK] phosphatase 1), which dephosphorylates and inactivates MAPKs. We investigated the role of DUSP1 in the antiinflammatory action of the GC dexamethasone (Dex). Dex-mediated inhibition of c-Jun N-terminal kinase and p38 MAPK was abrogated in DUSP1−/− mouse macrophages. Dex-mediated suppression of several proinflammatory genes (including tumor necrosis factor, cyclooxygenase 2, and interleukin 1α and 1β) was impaired in DUSP1−/− mouse macrophages, whereas other proinflammatory genes were inhibited by Dex in a DUSP1-independent manner. In vivo antiinflammatory effects of Dex on zymosan-induced inflammation were impaired in DUSP1−/− mice. Therefore, the expression of DUSP1 is required for the inhibition of proinflammatory signaling pathways by Dex in mouse macrophages. Furthermore, DUSP1 contributes to the antiinflammatory effects of Dex in vitro and in vivo.
PMCID: PMC2118371  PMID: 16880258
18.  IκB kinase (IKK)β, but not IKKα, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss 
The Journal of Experimental Medicine  2005;201(10):1677-1687.
Transcription factor, nuclear factor κB (NF-κB), is required for osteoclast formation in vivo and mice lacking both of the NF-κB p50 and p52 proteins are osteopetrotic. Here we address the relative roles of the two catalytic subunits of the IκB kinase (IKK) complex that mediate NF-κB activation, IKKα and IKKβ, in osteoclast formation and inflammation-induced bone loss. Our findings point out the importance of the IKKβ subunit as a transducer of signals from receptor activator of NF-κB (RANK) to NF-κB. Although IKKα is required for RANK ligand-induced osteoclast formation in vitro, it is not needed in vivo. However, IKKβ is required for osteoclastogenesis in vitro and in vivo. IKKβ also protects osteoclasts and their progenitors from tumor necrosis factor α–induced apoptosis, and its loss in hematopoietic cells prevents inflammation-induced bone loss.
PMCID: PMC2212920  PMID: 15897281

Results 1-18 (18)