A Novel Increase In Resistin Levels Induced By Tlr4 Deficiency Inhibits Lipopolysaccharide-Induced 1l-1 Beta And Tnf-Alpha Expression In C57bl/6j Mice

Background: The activation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) induces inflammatory cytokine production. Resistin is associated with chronic inflammation of the vascular system. However, the effects of TLR4 on resistin expression are not yet clear. Methods: Initially, resistin, IL-1 beta and TNF-alpha levels in wild type and TLR4-/- mice treated with or without LPS were examined using qPCR and ELISA, and the T lymphocyte profile was investigated using qPCR. Then, wild type C57BL/6J mice were intraperitoneally injected with hRetn alone or in combination with LPS, and IL-1 beta and TNF-alpha levels were examined using qPCR and ELISA. Results: Resistin was consistently highly expressed in the spleen and serum of TLR4-/- mice more than wild-type mice (P < 0.05). This expression pattern was significantly attenuated 24 h post intraperitoneal injection of 5 mg/kg LPS (P < 0.05). However, TNF-alpha and IL-1 beta levels did not increase and were not obviously altered by LPS treatment in TLR4-/- mice. Compared with the wild-type C57BL/6J mice, significantly increased levels of RORyt, FoxP3, Tbet and GATA3 mRNA that were observed in splenic lymphocytes from TLR4-/- mice using qPCR, and their levels significantly decreased following stimulation with 5 mg/kg LPS for 24 h (P < 0.05). Treatment with 25 mg/kg recombinant human resistin for 12 h deceased LPS-induced IL-1 beta and INF-alpha expression in wild-type C57BL/6J mice to some extent (P < 0.05). Conclusion: TLR4 deficiency increases resistin expression, while resistin inhibits LPS-induced IL-1 beta and TNF-alpha expression in C57BL/6J mice under some conditions.