IL-17 Stimulates the Production and Expression of Proinflammatory Cytokines, IL-β and TNF-α, by Human Macrophages

Dragan V Jovanovic; John A Di Battista; Johanne Martel-Pelletier; François C Jolicoeur; Yulan He; Mengkun Zhang; François Mineau; Jean-Pierre Pelletier

doi:10.4049/jimmunol.160.7.3513

journal article Apr 01, 1998

IL-17 Stimulates the Production and Expression of Proinflammatory Cytokines, IL-β and TNF-α, by Human Macrophages

Dragan V Jovanovic John A Di Battista Johanne Martel-Pelletier

François C Jolicoeur Yulan He Mengkun Zhang François Mineau Jean-Pierre Pelletier

The Journal of Immunology Vol. 160 No. 7 pp. 3513-3521 · Oxford University Press (OUP)

View at Publisher Save 10.4049/jimmunol.160.7.3513

Abstract

Abstract
IL-17 is a newly described, T cell-derived cytokine with ill-defined physiologic properties. As such, we examined the release of proinflammatory mediators by human macrophages in response to recombinant human (rh) IL-17. IL-1β and TNF-α expression and synthesis were up-regulated by rhIL-17 in a dose (ED50 was 50 ± 9 ng/ml)- and time-dependent fashion, with cytokine accumulation reaching a zenith after 9 h. Release of IL-6, PGE2, IL-10, IL-12, IL-1R antagonist, and stromelysin was also stimulated by rhIL-17. IL-1β and TNF-α mRNA expression levels were controlled by rhIL-17 in a complex manner with an initial 30-min inhibitory phase, and then up-regulation beginning at 1 h and reaching a plateau at about 3 h. The latter expression pattern closely mirrored the nuclear accumulation of the transcription factor nuclear factor-κB. cAMP mimetics isobutyl-1-methylxanthine (IBMX), forskolin, PGE2, and cholera toxin reversed rhIL-17-induced release of TNF-α, but had no consistent effect on induced IL-1β synthesis. Induced release of TNF-α was also inhibited by serine/threonine protein kinase inhibitors KT-5720 (protein kinase A) and Calphostin C (protein kinase C), mitogen-activated protein kinase kinase inhibitor PD098059, and a nonspecific tyrosine kinase inhibitor, genistein. Calphostin C alone abrogated the rhIL-17-induced release of IL-1β. The antiinflammatory cytokines IL-4 (p &lt; 0.01) and IL-10 (p &lt; 0.02) completely reversed rhIL-17-stimulated IL-1β release, while IL-13 and TGF-β2 were partially effective (59 and 43% diminution, respectively). IL-10 exerted a significant suppressive effect on IL-17-induced TNF-α release (99%, p &lt; 0.02), while the inhibitory effects of IL-4, IL-13, and TGF-β2 on TNF-α secretion were partial (48, 10, and 23%, respectively). The data suggest a pivotal role for IL-17 in initiating and/or sustaining an inflammatory response.

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Details

Published: Apr 01, 1998
Vol/Issue: 160(7)
Pages: 3513-3521
License: View

Authors

D

Dragan V Jovanovic