@article{52524b2684bd438fb1185ad10a425c0f,
title = "A mouse model for vitamin D-induced human cathelicidin antimicrobial peptide gene expression",
abstract = "In 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 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.",
keywords = "Cathelicidin, Cyp27b1, Innate immunity, Macrophage, TLR, Vitamin D",
author = "Lowry, {Malcolm B.} and Chunxiao Guo and Yang Zhang and Fantacone, {Mary L.} and Logan, {Isabelle E.} and Yan Campbell and Weijian Zhang and Mai Le and Indra, {Arup K.} and Gitali Ganguli-Indra and Jingwei Xie and Gallo, {Richard L.} and Koeffler, {H. Phillip} and Gombart, {Adrian F.}",
note = "Funding Information: We thank Tsuyako Saito and Sandra Uesugi for technical assistance and support (Oregon State University), and Birgitta Agerberth (Karolinska Institute, Stockholm, Sweden) and James Slauch (University of Illinois, Champaign Urbana, USA) for providing reagents. This study was supported by grants from the U.S. National Institutes of Health (NIH) National Cancer Institute 5R01CA26038 (HPK), National Institute of Allergy and Infectious Diseases 1R01AI065604-01A2 (AFG), National Center for Complementary and Integrative Health 5R01AT009168 (AFG) and National Institute of General Medical Sciences 5R01GM123081 (JX). We dedicate this study to Niels Borregaard who provided intellectual support, essential reagents and was a good friend and colleague. Funding Information: We thank Tsuyako Saito and Sandra Uesugi for technical assistance and support (Oregon State University), and Birgitta Agerberth (Karolinska Institute, Stockholm, Sweden) and James Slauch (University of Illinois, Champaign Urbana, USA) for providing reagents. This study was supported by grants from the U.S. National Institutes of Health (NIH) National Cancer Institute5R01CA26038 (HPK), National Institute of Allergy and Infectious Diseases1R01AI065604-01A2 (AFG), National Center for Complementary and Integrative Health5R01AT009168 (AFG) and National Institute of General Medical Sciences5R01GM123081 (JX). We dedicate this study to Niels Borregaard who provided intellectual support, essential reagents and was a good friend and colleague. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2020",
month = apr,
doi = "10.1016/j.jsbmb.2019.105552",
language = "English (US)",
volume = "198",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",
}