Interleukin-17 regulates chemokine and gelatinase B expression in fibroblasts to recruit both neutrophils and monocytes.
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.
Qiu
Zheng
Z
Rega Institute for Medical Research, University of Leuven, Belgium.
Dillen
Chris
C
Hu
Jialiang
J
Verbeke
Hannelien
H
Struyf
Sofie
S
Van Damme
Jo
J
Opdenakker
Ghislain
G
D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology
D018925:Chemokines; D020381:Interleukin-17; D012333:RNA, Messenger; D011994:Recombinant Proteins; D020780:Matrix Metalloproteinase 9