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: Beda Muehleisen, Daniel D Bikle, Carlos Aguilera, Douglas W Burton, George L Sen, Leonard J Deftos, Richard L Gallo
• Journal: Science translational medicine (Sci Transl Med) Vol. 4 Issue 135 Pg. 135ra66 (May 23 2012) ISSN: 1946-6242 [Electronic] United States
• PMID: 22623742 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antimicrobial Cationic Peptides
• Parathyroid Hormone
• Parathyroid Hormone-Related Protein
• Vitamin D
• Cathelicidins

Topics

• Animals
• Antimicrobial Cationic Peptides (metabolism)
• Mice
• Parathyroid Hormone (therapeutic use)
• Parathyroid Hormone-Related Protein (therapeutic use)
• Skin (drug effects, metabolism, microbiology)
• Skin Diseases, Bacterial (prevention & control)
• Vitamin D (therapeutic use)
• Cathelicidins