Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Iinterleukin(IL)-6 and tumor necrosis factor(TNF)-α play important roles in the pathogenesis of RA, however, it remains unclear how they affect or modulate the cell cycle of Rheumatoid Arthritis Fibroblast-Like Synoviocyte (RA-FLS). Cyclins, Cyclin-Dependent Kinases (CDKs) and CDK inhibitors (CDKIs) co-operate to regulate the cell cycle, and several conditions such as replicative senescence, irradiation, low serum culture and high cellular density culture are reported to induce the expression of CDKIs, including INK4 family and Cip/Kip family, resulting in inhibiting the growth of RA-FLS (Rheumatoid Arthritis Fibroblast-Like Synoviocyte) (1). In this study, we investigated the expression of Cell Cycle regulators under stimulations of IL-6 and TNF-α.
Methods: Under stimulations of IL-6/ soluble IL-6 receptor (100 ng/ml) or TNF-α (10ng/ml), total RNA and protein were extracted from RA-FLS to analyze expressions of CDK inhibitors(p16 INK4a , p21 Cip1 and p27 Kip1) by real-time PCR, and Cyclin D1 by Western Blot, respectively.
Results: Expressions of p16 INK4a was decreased by IL-6 stimulation and p27 Kip1 was increased by TNF-α, whereas p21 Cip1 was not changed. The expression of Cyclin D1 was increased by both of IL-6 and TNF-α.
Conclusion: In RA-FLS, IL-6 and TNF-α modulate the expression of p16 INK4a , p27 Kip1 genes, and induce the expression of Cyclin D1. Our results suggest IL-6 and TNF-α co-operate to drive the G1 to S phase transition in the cell cycle of RA-FLS. Reference: 1. Ken Taniguchi et al. nature medicine 1999 Jul;5(7):760-7.
To cite this abstract in AMA style:Kaneshiro K, Hashimoto T, Yoshida K, Nakai A, Hashimoto N, Suzuki K, Uchida K, Kawasaki Y, Nakagawa N, Shibanuma N, Sakai Y, Hashiramoto A. IL-6 and TNF-α Modulate Expressions of Cell Cycle Regulators of Rheumatoid Arthritis Fibroblast-like Synoviocytes [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/il-6-and-tnf-%ce%b1-modulate-expressions-of-cell-cycle-regulators-of-rheumatoid-arthritis-fibroblast-like-synoviocytes/. Accessed March 22, 2019.
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