Interleukin-19 downregulates interleukin-4-induced eotaxin production in human nasal fibroblasts

Allergol Int. 2011 Dec;60(4):449-57. doi: 10.2332/allergolint.10-OA-0262. Epub 2011 May 25.

Abstract

Background: Interleukin-19 (IL-19), a member of the IL-10 family, is characterized as the cytokine suppressing the release and function of several proinflammatory cytokines. For regulation of local reaction in allergic rhinitis (AR), IL-19 might play an especially important role.

Methods: We examined effects of IL-19 on IL-4-induced eotaxin production by human nasal fibroblasts. Early receptor-mediated events (expression of the suppressors of cytokine signaling (SOCS) and phosphorylation of signal transducer and activator of transcription 6 [STAT6]) by IL-19 was examined. Knockdown methods by RNAi were administered to investigate the involvement of those signal transductions.

Results: Pretreatment with IL-19 downregulates IL-4-induced eotaxin production, but not interferon-γ(IFN-γ)-induced RANTES. Pretreatment with IL-19 suppressed the IL-4-induced STAT6 phosphorylation. The IL-19 induced SOCS-1, but not SOCS-3 or SOCS-5. The SOCS-1 knockdown by RNAi diminished pretreatment with IL-19-induced down-regulation of eotaxin production.

Conclusions: These results suggest that IL-19 down-regulates IL-4-induced eotaxin production via SOCS-1 in human nasal fibroblasts. In non-hematopoietic cells in AR, IL-19 might be an immunosuppressive factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokines, CC / biosynthesis*
  • Down-Regulation / drug effects*
  • Fibroblasts / drug effects
  • Fibroblasts / immunology*
  • Gene Expression Regulation / drug effects
  • Gene Silencing
  • Humans
  • Interleukin-4 / antagonists & inhibitors*
  • Interleukin-4 / pharmacology
  • Interleukins / metabolism
  • Interleukins / pharmacology*
  • Nasal Mucosa / cytology
  • Nasal Mucosa / immunology*
  • Phosphorylation
  • RNA Interference
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism
  • STAT6 Transcription Factor / metabolism
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism

Substances

  • Chemokines, CC
  • IL19 protein, human
  • Interleukins
  • Receptors, Interleukin
  • SOCS1 protein, human
  • STAT6 Transcription Factor
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • interleukin-20 receptor
  • Interleukin-4