These authors contributed equally to this work.
Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids
Version of Record online: 14 SEP 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 3, pages 528–536, March 2014
How to Cite
Guo, C., Sinnott, B., Niu, B., Lowry, M. B., Fantacone, M. L. and Gombart, A. F. (2014), Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids. Mol. Nutr. Food Res., 58: 528–536. doi: 10.1002/mnfr.201300266
- Issue online: 4 MAR 2014
- Version of Record online: 14 SEP 2013
- Manuscript Accepted: 26 JUL 2013
- Manuscript Revised: 25 JUL 2013
- Manuscript Received: 12 APR 2013
- National Institutes of Health/National Institute of Allergy and Infectious Diseases. Grant Number: 5R01AI65604
- Cathelicidin antimicrobial peptide;
- Innate immunity;
- Vitamin D receptor
The cathelicidin antimicrobial peptide (CAMP) gene is induced by 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), lithocholic acid, curcumin, nicotinamide, and butyrate. Discovering additional small molecules that regulate its expression will identify new molecular mechanisms involved in CAMP regulation and increase understanding of how diet and nutrition can improve immune function.
Methods and results
We discovered that two stilbenoids, resveratrol and pterostilbene, induced CAMP promoter-luciferase expression. Synergistic activation was observed when either stilbenoid was combined with 1α,25(OH)2D3. Both stilbenoids increased CAMP mRNA and protein levels in the monocyte cell line U937 and synergy was observed in both U937 and the keratinocyte cell line, HaCaT. Inhibition of resveratrol targets sirtuin-1, cyclic AMP production and the c-Jun N-terminal, phosphoinositide 3 and AMP-activated kinases did not block induction of CAMP by resveratrol or synergy with 1α,25(OH)2D3. Nevertheless, inhibition of the extracellular signal regulated 1/2 and p38 mitogen-activated protein kinases, increased CAMP gene expression in combination with 1α,25(OH)2D3 suggesting that inhibition of these kinases by resveratrol may explain, in part, its synergy with vitamin D.
Our findings demonstrate for the first time that stilbenoid compounds may have the potential to boost the innate immune response by increasing CAMP gene expression, particularly in combination with 1α,25(OH)2D3.