Session Type: Abstract Submissions (ACR)
Oncostatin M (OSM) is a pleiotropic cytokine that belongs to the interleukin(IL)-6 group of cytokines. High level of OSM were detected in synoviums of rheumatoid arthritis (RA) patients but its exact role in arthritis perpetuation has not been elucidated. We evaluated the role of OSM in T helper 17(Th17) cell differentiation, the most important cells in arthritis development.
Collagen-induced arthritis (CIA) was induced in DBA/1J mice. IL-2 immune complex(IC) were injected intraperitoneally three times at 2days intervals before 1st immunization. Severity of arthritis was assessed by clinical scoring of arthritis. CD4+ T cells were isolated by MACS and incubated in Th17 differentiation condition with and without OSM. The levels of cytokines were measured using ELISA. To analyze intracellular cytokine were analyed by FACS. Subpopulations of T cells of spleens were assessed by confocal microscopy. The mRNA levels of OSM and signaling molecules were determined by RT-PCR and real time PCR. The protein levels were assessed by Western blot. Suppressor of cytokine signaling3 (SOCS3) small interfering RNA(siRNA) was transfected by using the Amaxa 4D-nucleofector X unit (Lonxa, Cologne, Germany).
IL-2IC treatment reduced the clinical arthritis score and OSM and SOCS were increased in spleens of IL-21C treated mice. We observed that OSM suppressed Th17 cell differentiation and the levels of IL-17 and IL-21 were decreased in dose dependent manner in vitro. OSM time dependently increase the level of STAT3, STAT5 and SOCS3 in mRNA and protein levels. STA21, the STAT3 inhibitor abrogated the suppressive effect of OSM on Th17 differentiation. SOCS3 siRNA also abrogated the suppressive effect of OSM.
OSM was up-regulated spleens of IL-2IC treated mice. OSM suppressed the Th17cell differentiation and the inhibitory effects of OSM on Th17 cells were via SCOS3 regulation.
Y. O. Jung,
S. Y. Lee,
S. Y. Lee,
M. L. Cho,
H. J. Son,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/oncostatin-m-suppresses-activation-of-il-17th17-via-suppressor-of-cytokine-signaling3-socs3-regulation-in-cd4-t-cells/