Vitamin D3 Induces Autophagy in Human Monocytes/Macrophages via Cathelicidin

作者：Yuk Jae Min; Shin Dong Min; Lee Hye Mi; Yang Chul Su; Jin Hyo Sun; Kim Kwang Kyu; Lee Zee Won; Lee Sang Hee; Kim Jin Man; Jo Eun Kyeong^*

来源：Cell Host & Microbe, 2009, 6(3): 231-243.

DOI：10.1016/j.chom.2009.08.004

Autophagy and vitamin D3-mediated innate immunity have been shown to confer protection against infection with intracellular Mycobacterium tuberculosis. Here, we show that these two antimycobacterial defenses are physiologically linked via a regulatory function of human cathelicidin (hCAP-18/LL-37), a member of the cathelicidin family of antimicrobial proteins. We show that 1,25-dihydroxyvitamin D (1,25D3), the active form of vitamin D, induced autophagy in human monocytes via cathelicidin, which activated transcription of the autophagy-related genes Beclin-1 and Atg5. 1,25D3 also induced the colocalization of mycobacterial phagosomes with autophagosomes in human macrophages in a cathelicidin-dependent manner. Furthermore, the antimycobacterial activity in human macrophages mediated by physiological levels of 1,25D3 required autophagy and cathelicidin. These results indicate that human cathelicidin, a protein that has direct antimicrobial activity, also serves as a mediator of vitamin D3-induced autophagy.

• 出版日期2009-9-17