A mouse model for vitamin D-induced human cathelicidin antimicrobial peptide gene expression

Publication date: Available online 26 November 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Malcolm B. Lowry, Chunxiao Guo, Yang Zhang, Mary L. Fantacone, Isabelle E. Logan, Yan Campbell, Weijian Zhang, Mai Le, Arup K. Indra, Gitali Ganguli-Indra, Jingwei Xie, Richard L. Gallo, H. Phillip Koeffler, Adrian F. GombartAbstractIn humans and other primates, 1,25(OH)2vitamin D3 regulates the expression of the cathelicidin antimicrobial peptide (CAMP) gene via toll-like receptor (TLR) signaling that activates the vitamin D pathway. Mice and other mammals lack the vitamin D response element (VDRE) in their CAMP promoters. To elucidate the biological importance of this pathway, we generated transgenic mice that carry a genomic DNA fragment encompassing the entire human CAMP gene and crossed them with Camp knockout (KO) mice. We observed expression of the human transgene in various tissues and innate immune cells. However, in mouse CAMP transgenic macrophages, TLR activation in the presence of 25(OH)D3 did not induce expression of either CAMP or CYP27B1 as would normally occur in human macrophages, reinforcing important species differences in the actions of vitamin D. Transgenic mice did show increased resistance to colonization by Salmonella typhimurium in the gut. Furthermore, the human CAMP gene restored wound healing in the skin of Camp KO mice. Topical application of 1,25(OH)2vitamin D3 to the skin of CAMP transgenic mice induced CAMP expression ...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research