Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism

J. Clin. Invest. 117:803-811 (2007)

Speaker：黃炫榕                                                                   Time：13:10 ~ 14:00, May. 2, 2007

Commentator：王志堯 醫師                        Place：Room 601

Abstract:

        Injury triggers keratinocytes to migrate and reestablish an physical barrier. It is important for the wound micro-milieu against infection before the formation of the barrier. Antimicrobial peptides (AMPs) such as cathelicidin are essential to the process, but the elements responsible for control of expression during injury were still unknown. This paper demonstrated that vitamin D₃ plays a role in innate defense during wound repair. At first, the authors found that injury triggers increase in 1,25D₃ signaling molecules includingcathelicidin, TLR2, CD14, and the vitamin D₃ catabolic enzyme CYP24A1 in keratinocytes. CYP27B1, the enzyme responsible for converting inactive 25D₃ to active 1,25D_3, is also increased by injury. This induction may follow the soluble factors present in wound, such as TGF-b1, or by microbial stimulation of TLR2. Wounds in the CYP27B1-deficiency mice failed to induce 1,25D₃-regulated CD14 expression in contrast to wild-type mice. Furthermore, 1,25D₃ enhances TLR2 function to respond to microbial components such as Malp-2 orzymosan in a dose-dependent manner. Finally, a functional vitamin D-responsive elements (VDRE) was required for transactivation of cathelicidin by Malp-2 and 1,25D₃, and inhibition of the vitamin D receptor (VDR) blocked Malp-2-induced cathelicidin. Therefore, the results illustrated that injury enhances vitamin D₃ metabolism and related genes, which led to increase AMP response. This elegant regulation protects wounds from infection. Whether disturbed vitamin D₃ metabolism after wounding leads abnormal wound repair or infection may need further investigation.

References:

1.          Jurgen Schauber, et al. 2007. Injury enhances TLR2 fuction and antimicrobial peptide expresuion through a vitamin D-dependent mechanism. J. Clin. Invest. 117:803-811.

2.          Liu, P.T., et al. 2006. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 311:1770–1773.