Vitamin D in defense of the human immune response.
Defensin is a generic name reserved for an endogenously synthesized antimicrobial agent. The purpose of this review is to describe a series of discoveries that led to the proposal that 25-hydroxylated metabolites of vitamin D are key, intracellular regulators of the synthesis and action of naturally occurring defensin molecules against bacterial antigens. The discussion will (1) highlight the basic elements of human immune response that is responsive to vitamin D, (2) recount work relevant to the extrarenal expression of the vitamin D-1-hydroxlase (CYP27b1) in the macrophage as an initiator of the innate immune response, and (3) describe recent work on the relevance of the vitamin D intracrine-autocrine-paracrine system in a model of a common and devastating human disease, tuberculosis.
Division of Endocrinology, Diabetes and Metabolism, Burns and Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room B-131, Los Angeles, CA 90048, USA. adamsj@cshs.org
John S
JS
Adams
Philip T
PT
Liu
Rene
R
Chun
Robert L
RL
Modlin
Martin
M
Hewison
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000502:physiology; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000502:physiology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D014376:Tuberculosis / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism / Q000502:physiology*; D014815:Vitamins / Q000378:metabolism
D000890:Anti-Infective Agents; D014815:Vitamins; D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase