NF-κB-dependent induction of cathelicidin-related antimicrobial peptide in murine mast cells by lipopolysaccharide

Guiming Li, Joanne Domenico, Yi Jia, Joseph J. Lucas, Erwin W. Gelfand

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background: An important aspect of the innate immune response to pathogens is the production of anti-microbial peptides such as cathelicidin-related antimicrobial peptide (CRAMP), the murine homologue of human cathelicidin LL-37. In this study, mechanisms regulating LPS-induction of CRAMP gene expression in mast cells were investigated. NF-κB and MAPK pathways were the focus of investigation. Methods: Mouse bone marrow-derived mast cells were grown in culture and stimulated with LPS. MAPKs and NF-κB were monitored by immunoblot analysis. ERK, JNK and p38 MAPK were inhibited using siRNAs or a pharmacological inhibitor. Accumulation of the p65 component of NF-κB was inhibited by siRNA and NF-κB activation was inhibited by overexpression of IκBα. MEKK2 or MEKK3 were overexpressed by transfection. The effects of all of these treatments on CRAMP gene expression were monitored by RT-PCR. Results: Inhibition of ERK, JNK or p38 MAPK had little discernible effect on LPS-inducible CRAMP gene expression. Overexpression of MEKK2 or MEKK3 likewise had little impact. However, inhibition of the accumulation of p65 NF-κB prevented LPS-induced CRAMP mRNA. An important role for NF-κB in CRAMP gene expression was confirmed by overexpression of IκBα, which reduced both basal and induced levels of CRAMP mRNA. Conclusions: NF-κB, but not MAPKs, plays an important role in LPS-mediated induction of CRAMP gene in mast cells. Defects which inhibit NF-κB activity may increase susceptibility to bacterial and viral pathogens which are sensitive to cathelicidins.

Original languageEnglish (US)
Pages (from-to)122-132
Number of pages11
JournalInternational Archives of Allergy and Immunology
Volume150
Issue number2
DOIs
StatePublished - Sep 2009

Keywords

  • Cathelicidin-related antimicrobial peptide
  • Inflammation
  • Mast cells
  • Transcription factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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