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Logo of bmcimmBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Immunology
 
BMC Immunol. 2012; 13: 19.
Published online Apr 14, 2012. doi:  10.1186/1471-2172-13-19
PMCID: PMC3353220
High glucose concentrations induce TNF-α production through the down-regulation of CD33 in primary human monocytes
Yolanda Gonzalez,1 M Teresa Herrera,1 Gloria Soldevila,3 Lourdes Garcia-Garcia,4 Guadalupe Fabián,2 E Martha Pérez-Armendariz,5 Karen Bobadilla,1 Silvia Guzmán-Beltrán,1 Eduardo Sada,1 and Martha Torrescorresponding author1
1Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, Calzada de Tlalpan 4502, Sección XVI, Ciudad de México, 14080, México
2Clínica del Síndrome Metabólico, Instituto Nacional de Enfermedades Respiratorias, Calzada de Tlalpan 4502, Sección XVI, Ciudad de México, 14080, México
3Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria 04510, Ciudad de México, 70228, México
4Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Av. Universidad 655, Cuernavaca, 62508, M&#233xico
5Departamento de Medicina Experimental, Universidad Nacional Autónoma de México, Ciudad Universitaria 04510, Ciudad de México, 70228, México
corresponding authorCorresponding author.
Yolanda Gonzalez: yolag/at/hotmail.com; M Teresa Herrera: marieteresah/at/yahoo.com; Gloria Soldevila: soldevi/at/servidor.unam.mx; Lourdes Garcia-Garcia: garcigarml/at/gmail.com; Guadalupe Fabián: lupitafabian/at/gmail.com; E Martha Pérez-Armendariz: mperezarmendariz/at/aol.com; Karen Bobadilla: karenbolo/at/yahoo.com.mx; Silvia Guzmán-Beltrán: guzman.silvia/at/gmail.com; Eduardo Sada: eduardosadadiaz/at/yahoo.com; Martha Torres: marthatorres98/at/yahoo.com
Received December 8, 2011; Accepted April 14, 2012.
Abstract
Background
CD33 is a membrane receptor containing a lectin domain and a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) that is able to inhibit cytokine production. CD33 is expressed by monocytes, and reduced expression of CD33 correlates with augmented production of inflammatory cytokines, such as IL-1β, TNF-α, and IL-8. However, the role of CD33 in the inflammation associated with hyperglycemia and diabetes is unknown. Therefore, we studied CD33 expression and inflammatory cytokine secretion in freshly isolated monocytes from patients with type 2 diabetes. To evaluate the effects of hyperglycemia, monocytes from healthy donors were cultured with different glucose concentrations (15-50 mmol/l D-glucose), and CD33 expression and inflammatory cytokine production were assessed. The expression of suppressor of cytokine signaling protein-3 (SOCS-3) and the generation of reactive oxygen species (ROS) were also evaluated to address the cellular mechanisms involved in the down-regulation of CD33.
Results
CD33 expression was significantly decreased in monocytes from patients with type 2 diabetes, and higher levels of TNF-α, IL-8 and IL-12p70 were detected in the plasma of patients compared to healthy donors. Under high glucose conditions, CD33 protein and mRNA expression was significantly decreased, whereas spontaneous TNF-α secretion and SOCS-3 mRNA expression were increased in monocytes from healthy donors. Furthermore, the down-regulation of CD33 and increase in TNF-α production were prevented when monocytes were treated with the antioxidant α-tocopherol and cultured under high glucose conditions.
Conclusion
Our results suggest that hyperglycemia down-regulates CD33 expression and triggers the spontaneous secretion of TNF-α by peripheral monocytes. This phenomenon involves the generation of ROS and the up-regulation of SOCS-3. These observations support the importance of blood glucose control for maintaining innate immune function and suggest the participation of CD33 in the inflammatory profile associated with type 2 diabetes.
Keywords: Antioxidant, Cytokines, Monocytes, ROS, Siaglec-3, Type 2 diabetes
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