title: PTH/PTHrP and vitamin D control antimicrobial peptide expression and susceptibility to bacterial skin infection.
abstract: The production of antimicrobial peptides is essential for protection against a wide variety of microbial pathogens and plays an important role in the pathogenesis of several diseases. The mechanisms responsible for expression of antimicrobial peptides are incompletely understood, but a role for vitamin D as a transcriptional inducer of the antimicrobial peptide cathelicidin has been proposed. We show that 1,25-dihydroxyvitamin D(3) (1,25-D3) acts together with parathyroid hormone (PTH), or the shared amino-terminal domain of PTH-related peptide (PTHrP), to synergistically increase cathelicidin and immune defense. Administration of PTH to mouse skin decreased susceptibility to skin infection by group A Streptococcus. Mice on dietary vitamin D(3) restriction that responded with an elevation in PTH have an increased risk of infection if they lack 1,25-D3. These results identify PTH/PTHrP as a variable that serves to compensate for inadequate vitamin D during activation of antimicrobial peptide production.
authors.affiliation: Division of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Beda
authors.initials: B
authors.lastname: Muehleisen
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Bikle
authors.forename: Carlos
authors.initials: C
authors.lastname: Aguilera
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Burton
authors.forename: George L
authors.initials: GL
authors.lastname: Sen
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Deftos
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D051379:Mice; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D044162:Parathyroid Hormone-Related Protein / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology*; D017192:Skin Diseases, Bacterial / Q000517:prevention & control*; D014807:Vitamin D / Q000627:therapeutic use*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D014807:Vitamin D; D054804:Cathelicidins