TLR4 mediates LPS-induced HO-1 expression in mouse liver:Role of TNF-α and IL-1β

AIM:Heine oxygenase (HO)-I catalyzes the conversion ofheme to biliverdin,iron and carbon monoxide.HO-1 isinduced by many stimuli including heine,Hb,heat stress,lipopolysaccharide (LPS) and cytokines.Previous studiesdemonstrated that LPS induced HO-1 gene activation andHO-1 expression in liver.However,the mechanisms of LPS-induced HO-1 expression in liver remain unknown.The effectof toll-like receptor-4 (TLR4) on LPS-induced liver HO-1expression and the role of TNF-α and IL-1β in this conditionwere determined.METHODS:HO-1 expression was determined byimmunofluorescent staining and immunoblotting.Doubleimmunofluorescent staining was performed to determine thecell type of HO-1 expression in liver.RESULTS:A low dose of LPS significantly increased HO-1expression in the liver which was localized in Kupffer cellsonly.Furthermore,HO-1 expression was enhanced by threedoses of LPS.HO-1 expression was significantly inhibitedin the liver of TLR4 mutant mice.While the liver HO-1expression in TNF KO mice was much lower than that inC57 mice following the same LPS treatment,IL-1β KO hada slight influence on liver HO-1 expression following LPStreatment.CONCLUSION: The present results confirm that macrophages are the major source of HO-1 in the liver induced by LPS. This study demonstrates that TLR4 plays a dominant role in mediating HO-1 expression following LPS. LPS-induced HO-1 expression is mainly mediated by endogenous TNF-a, but only partially by endogenous IL-lβ.