INDUCTION OF INNATE IMMUNITY BY VITAMIN D3 AND ITS ANALOGS

摘要

Cationic antimicrobial peptides (AMPs) are an integral part of the innate immune system. Cathelicidin and defensin homologs from a variety of species exhibit broad-range bactericidal activity. The human cathelicidin analog, hCAP18, is encoded by the CAMP gene. Vitamin D3 and its analogs upregulate transcription of CAMP and defensin ß2 (defB2) genes, leading to increased expression of hCAP18 mRNA and defB2. Induction of CAMP was observed in acute myeloid leukemia (AML), immortalized keratinocyte and colon cancer cell lines, as well as normal human bone marrow (BM)-derived macrophages and fresh BM cells. The present invention provides methods of inducing cathelicidin production by administering Vitamin D3 or Vitamin D3 analogs, as well as methods of treating skin infections and infections of the colon, sepsis and wound healing, preventing bacterial growth on skin grafts, promoting angiogenesis, and promoting chemoattraction by administering Vitamin D3 or Vitamin D3 analogs to upregulate cathelicidin and defensin expression.