Upregulation of stromal cell-derived factor by IL-17 and IL-18 via a phosphatidylinositol 3-kinase-dependent pathway.
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.
Rheumatism Research Center (RhRC), Catholic Institute of Medical Sciences, The Catholic University of Korea, Seoul, Korea.
I E
IE
Ahn
J H
JH
Ju
S Y
SY
Lee
J S
JS
Park
H J
HJ
Oh
H R
HR
Kim
S H
SH
Lee
S H
SH
Park
H Y
HY
Kim
M L
ML
Cho
D057134:Antibodies, Neutralizing / Q000494:pharmacology; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000276:immunology; D004357:Drug Synergism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D058539:Phosphatidylinositol 3-Kinase / Q000276:immunology / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D061251:Primary Cell Culture; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
D057134:Antibodies, Neutralizing; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D020381:Interleukin-17; D020382:Interleukin-18; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D058539:Phosphatidylinositol 3-Kinase