Human beta-defensin 3 has immunosuppressive activity in vitro and in vivo

Fiona Semple, Sheila Webb, Hsin-Ni Li, Hetal B. Patel, Mauro Perretti, Ian J. Jackson, Mohini Gray, Donald J. Davidson, Julia Dorin

Research output: Contribution to journalArticlepeer-review

Abstract

beta-defensins are antimicrobial peptides with an essential role in the innate immune response. In addition beta-defensins can also chemoattract cells involved in adaptive immunity. Until now, based on evidence from dendritic cell stimulation, human beta defensin-3 (hBD3) was considered pro-inflammatory. We present evidence here that hBD3 lacks pro-inflammatory activity in human and mouse primary M phi. In addition, in the presence of LPS, hBD3 and the murine orthologue Defb14 (but not hBD2), effectively inhibit TNF-alpha and IL-6 accumulation implying an anti-inflammatory function. hBD3 also inhibits CD40/IFN-gamma stimulation of M phi and in vivo, hBD3 significantly reduces the LPS-induced TNF-alpha level in serum. Recent work has revealed that hBD3 binds melanocortin receptors but we provide evidence that these are not involved in hBD3 immunomodulatory activity. This implies a dual role for hBD3 in antimicrobial activity and resolution of inflammation.

Original languageEnglish
Pages (from-to)1073-1078
Number of pages6
JournalEuropean Journal of Immunology
Volume40
Issue number4
DOIs
Publication statusPublished - Apr 2010

Keywords

  • Anti-inflammatory
  • cAMP
  • Defensin
  • TNF-a

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