title: Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids.
abstract: METHODS
  The cathelicidin antimicrobial peptide (CAMP) gene is induced by 1α,25-dihydroxyvitamin D3 (1α,25(OH)2 D3), 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.
  
  
  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)2 D3. 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)2 D3. 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)2 D3 suggesting that inhibition of these kinases by resveratrol may explain, in part, its synergy with vitamin D.
  
  
  CONCLUSIONS
  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)2 D3.
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331.|Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331.|Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331.
authors.forename: Brian
authors.initials: B
authors.lastname: Sinnott
authors.affiliation: School of Medicine, Oregon Health Sciences University, Portland, Oregon 97239.
authors.forename: Brenda
authors.initials: B
authors.lastname: Niu
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331.|Department of Microbiology, Oregon State University, Corvallis, Oregon 97331.
authors.forename: Malcolm B
authors.initials: MB
authors.lastname: Lowry
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331.|Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Fantacone
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331.|Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Gombart
mesh_terms: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D054852:Small Molecule Libraries; D013267:Stilbenes; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; C107773:pterostilbene; D000242:Cyclic AMP; D048051:p38 Mitogen-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: Cathelicidin antimicrobial peptide; Innate immunity; Resveratrol; Stilbenoid; Vitamin D receptor
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