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Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids

Authors

  • Chunxiao Guo,

    1. Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    2. Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, USA
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    • These authors contributed equally to this work.

  • Brian Sinnott,

    1. Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    2. Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, USA
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    • These authors contributed equally to this work.

  • Brenda Niu,

    1. School of Medicine, Oregon Health Sciences University, Portland, OR, USA
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  • Malcolm B. Lowry,

    1. Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    2. Department of Microbiology, Oregon State University, Corvallis, OR, USA
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  • Mary L. Fantacone,

    1. Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    2. Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, USA
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  • Adrian F. Gombart

    Corresponding author
    1. Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    2. Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, USA
    • Correspondence: Professor Adrian F. Gombart, Linus Pauling Institute, 307 Linus Pauling Science Center, Corvallis, OR 97331, USA

      E-mail: adrian.gombart@oregonstate.edu

      Fax: +1-541-737-5077

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Abstract

Scope

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.

Conclusion

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.

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