Various proinflammatory cytokines have been demonstrated to be involved in insulin resistance and other obesity related diseases. Preadipocytes and adipocytes are likely to modulate inflammatory and immune processes by intrinsic mechanisms. Toll-like receptors (TLRs) which are together with CD14 involved in the innate immunity and are able to recognize microbial components. Microbial components and immunosuppressive drugs modulate the cytokine expression. We address here the influence of immunosuppressive drugs and microbial components (lipopolysaccharide [LPS], lipoteichoic Acid [LTA] and Pam-3-Cys) of TLR2-, TLR4-, IL-6- and TNFα expression. The regulation of TLRs and cytokine mRNA levels was investigated by using the TaqMan quantitative PCR method. To detect the possible pro- or anti-inflammatory effects of microbial components and immunosuppressive drugs we measured the IL-6- and TNFα expression in 3T3-L1 adipocytes by TaqMan quantitative PCR and its secretion by ELISA, respectively. 3T3-L1 adipocytes expressed TLR2, TLR4, IL-6- and TNFα on mRNA and protein levels, as detected by RT-PCR and immunocytochemistry. LPS enhanced the TLR4 and cytokine expression, while LTA barely regulated the expression of TLRs and cytokines. Pam-3-Cys induced TLR2 and cytokine expression. Dexamethasone inhibited TLR and cytokine expression. We provide evidence that TLRs can activate the pathway of innate immunity in adipocytes which result in the secretion of immunomodulatory molecules. The pharmacological regulation of TLR and cytokine expression may provide a novel mechanism in the treatment of insulin resistance and other obesity related diseases.
01 - 05 Apr 2006
European Society of Endocrinology