Interleukin-17 regulates chemokine and gelatinase B expression in fibroblasts to recruit both neutrophils and monocytes

Immunobiology. 2009;214(9-10):835-42. doi: 10.1016/j.imbio.2009.06.007. Epub 2009 Jul 22.

Abstract

Interleukin 17 (IL-17) is a proinflammatory cytokine, produced only by activated lymphocytes, but with a broad cellular host range. The effects of IL-17 on fibroblasts were investigated by analysis of the induction of chemokine and matrix metalloprotease (MMP) mRNA levels by RT-PCR. IL-17 stimulated CC chemokine (monocyte chemotactic protein-1; MCP-1/JE) and CXC (KC, MIP-2) chemokine and TIMP-1 mRNA expression in fibroblastoid L929 cells. In normal mouse embryonic fibroblasts (MEF) this induction profile by IL-17 was extended with the mRNAs encoding the chemokine granulocyte chemotactic protein-2 (GCP-2) and the proteases MMP-3, MMP-9 and MMP-13. The MMP-9 and GCP-2 induction by IL-17 in MEF, and the absence of induction in L929 cells, were corroborated by gelatin zymography and ELISA, respectively. The induction of MCP-1/CCL2 by IL-17 was confirmed in human diploid fibroblasts. We conclude that IL-17 regulates differentially chemokine and MMP expression by normal and transformed fibroblasts and is indirectly capable of attracting both monocytes and neutrophils to the inflammatory focus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Dose-Response Relationship, Immunologic
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Fibroblasts / immunology*
  • Humans
  • Interleukin-17 / pharmacology
  • Interleukin-17 / physiology*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Monocytes / metabolism*
  • Neutrophils / metabolism*
  • RNA, Messenger / analysis
  • Recombinant Proteins / pharmacology

Substances

  • Chemokines
  • Interleukin-17
  • RNA, Messenger
  • Recombinant Proteins
  • Matrix Metalloproteinase 9