Gene expressions of Toll-like receptor 2, but not toll-like receptor 4, isinduced by LPS and inflammatory cytokines in mouse macrophages

Toll-like receptors (TLRs) are a family of mammalian homologues of Drosophi la Toll and play important roles in host defense. Two of the TLRs, TLR2 and TLR4, mediate the responsiveness to LPS, Here the gene expression of TLR2 and TLR4 was analyzed in mouse macrophages, Mouse splenic macrophages respo nded to an intraperitoneal injection or in vitro treatment of LPS by increa sed gene expression of TLR2, but not TLR4. Treatment of a mouse macrophage cell line with LPS, synthetic lipid A, IL-2, IL-15, IL-1 beta, IFN-gamma, o r TNF-alpha significantly increased TLR2 mRNA expression, whereas TLR4 mRNA expression remained constant. TLR2 mRNA increase in response to synthetic lipid A was severely impaired in splenic macrophages isolated from TLR4-mut ated C3H/HeJ mire, suggesting that TLR4 plays an essential role in the proc ess. Specific inhibitors of mitogen-activated protein/extracellular signal- regulated kinase kinase and p38 kinase did not significantly inhibit TLR2 m RNA up-regulation by LPS, In contrast, LPS-mediated TLR2 mRNA induction was abrogated by pretreatment with a high concentration of curcumin, suggestin g that NP-kappaB activation may be essential for the process. Taken togethe r, our results indicate that TLR2, in contrast to TLR4, can be induced in m acrophages in response to bacterial infections and mag accelerate the innat e immunity against pathogens.