Increased MAPK and NF-κB expression of Langerhans cells is dependent on TLR2 and TLR4, and increased IRF-3 expression is partially dependent on TLR4 following UV exposure

Abstract

Toll-like receptors (TLRs) and epidermal Langerhans cells (LCs) play a crucial role in innate and adaptive immunity. To date, the pattern of TLR expression has not been fully analyzed. The effects of ultraviolet (UV) light on TLR expression and the downstream signaling cascades of human LC have not been examined. In this study, we purified human epidermal LCs using a density gradient centrifugation method and an immunomagnetic microbead method. We found that cultured purified LCs from human skin express mRNAs encoding TLR2, TLR4, TLR5 and TLR7-9. The expression of TLR2 and TLR4 protein was confirmed by Western blot analysis. The results showed for the first time that UV exposure up-regulated the mRNA and protein expression of TLR2 and TLR4 in human LCs. We also found that UV exposure-induced up-regulated MAPK and NF-κB/p65 expression was dependent on TLR2 and TLR4, and up-regulated IRF-3 expression was partially dependent on TLR4. In conclusion, UV light up-regulates the expression of TLR2, TLR4 and downstream signaling molecules MAPK, NF-κB/p65 and IRF-3 in human LCs. This suggests that UV light has a significant effect on skin immune responses.