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Upregulation of Stromal Cell–Derived Factor By IL‐17 and IL‐18 Via a Phosphatidylinositol 3‐Kinase‐Dependent Pathway
Author(s) -
Ahn I. E.,
Ju J. H.,
Lee S. Y.,
Park J. S.,
Oh H. J.,
Kim H. R.,
Lee S. H.,
Park S. H.,
Kim H. Y.,
Cho M. L.
Publication year - 2012
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2012.02745.x
Subject(s) - pi3k/akt/mtor pathway , interleukin , downregulation and upregulation , stromal cell , immune system , inflammation , biology , chemistry , cancer research , immunology , microbiology and biotechnology , cytokine , signal transduction , gene , biochemistry
Th17 cells that produce interleukin (IL)‐17 play a key role in the pathogenesis of autoimmune inflammation. Among the various cytokines that are involved in the IL‐17 pathway, members of the IL‐1β family, including IL‐18, have recently gained attention. In this study, we stimulated synovial fibroblasts with a combination of IL‐17 and IL‐18 and quantified their stromal cell–derived factor‐1 (SDF‐1) production by enzyme‐linked immunosorbent assay and their transcript levels by reverse transcription–polymerase chain reaction. Both IL‐17 and IL‐18 significantly increased the level of SDF‐1, not only individually but also synergistically ( P < 0.05). The synergism was effectively suppressed by anti‐IL‐17 and ‐IL‐18 antibodies, and a PI3K inhibitor. To the best of our knowledge, this is the first report of PI3K‐dependent synergism between IL‐18 and IL‐17, and this work adds a novel perspective of the role of IL‐18 in immune regulation. The individual effects of these two cytokines, and their interactions, suggest an interrelationship between the IL‐1 family and IL‐17.