TitleA mouse model for vitamin D-induced human cathelicidin antimicrobial peptide gene expression.
Publication TypeJournal Article
Year of Publication2019
AuthorsLowry MB, Guo C, Zhang Y, Fantacone ML, Logan IE, Campbell Y, Zhang W, Le M, Indra AK, Ganguli-Indra G, Xie J, Gallo RL, H Koeffler P, Gombart AF
JournalJ Steroid Biochem Mol Biol
Date Published2019 Nov 26

In humans and other primates, 1,25(OH)vitamin D 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)D 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)vitamin D to the skin of CAMP transgenic mice induced CAMP expression and increased killing of Staphylococcus aureus in a wound infection model. Our model can help elucidate the biological importance of the vitamin D-cathelicidin pathway in both pathogenic and non-pathogenic states.

Alternate JournalJ. Steroid Biochem. Mol. Biol.
PubMed ID31783153
Grant ListR01 AI065604 / AI / NIAID NIH HHS / United States
R01 AT009168 / AT / NCCIH NIH HHS / United States