Stimulation with Resistin Upregulates Chemokine Production By Fibroblast-like Synoviocytes from Patients with Rheumtoid Arthritis

Hiroshi Sato¹, Sei Muraoka¹, Natsuko Kusunoki¹, Shotaro Masuoka¹, Soichi Yamada¹, Toshio Imai², Shinichi Kawai³ and Toshihiro Nanki¹, ¹Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan, ²KAN Research Institute, Inc., Kobe, Japan, ³Department of Inflammation and Pain Control Research, Toho University School of Medicine, Tokyo, Japan

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Adipokines, chemokines and rheumatoid arthritis (RA)

Session Information

Date: Monday, November 6, 2017

Title: Rheumatoid Arthritis – Human Etiology and Pathogenesis Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Adipose tissue synthesizes and releases physiologically active molecules that are known as adipokines. Resistin, an adipokine, has been widely studied the regulation of glucose homeostasis and insulin sensitivity. Moreover, resistin also plays an important role of inflammation. We previously reported that serum level of resistin correlated with the disease activity of rheumatoid arthritis (RA). However, the pathogenic role of resistin has not been elucidated. In this study, we examined the stimulatory effect of resistin on fibroblast-like synoviocytes (FLSs) form RA patients.

Methods: Expression of resistin and the receptor, adenylyl cyclase-associated protein 1 (CAP1), in the synovial tissue from RA and osteoarthritis (OA) was examined by immunohistochemistry. FLSs were incubated with resistin for 18 hours. Then, total RNA was extracted, and the gene expression profile was analyzed by RNA sequencing. Concentration of chemokines in the culture supernatant was determined by enzyme-linked immunosorbent assay (ELISA). Expression of CAP1 was examined by RT-PCR and Western blotting. To verify signaling of resistin, we pretreated FLSs with a PKA inhibitor, KT5720, or transfected siRNA for CAP1 before stimulation with resistin.

Results: Resistin and CAP1 was abundantly expressed in the RA synovial tissue. Resistin expression was minimal in the OA synovium. Double immunofluorescence staining revealed that CD68-positive macrophages expressed resistin in RA synovium. CAP1 was expressed by cadherin-11-positive FLSs in RA. RT-PCR and Western blotting showed that in vitro cultured FLSs also expressed CAP1. RNA sequencing revealed that expressions of 18 genes, including 7 chemokines (CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8 and CCL2), from RA FLSs were increased more than 2 folds by stimulation with resistin. Production of CXCL8 and CCL2 in the culture supernatant of FLSs was increased by resistin. Pretreatment with KT5720 or transfection with CAP1 siRNA suppressed resistin-induced CXCL8 production by FLSs.

Conclusion: Resistin might play an important role in the pathogenesis of RA via upregulation of chemokine production in the synovial tissue.

Disclosure: H. Sato, None; S. Muraoka, None; N. Kusunoki, None; S. Masuoka, None; S. Yamada, None; T. Imai, None; S. Kawai, None; T. Nanki, None.

To cite this abstract in AMA style:

Sato H, Muraoka S, Kusunoki N, Masuoka S, Yamada S, Imai T, Kawai S, Nanki T. Stimulation with Resistin Upregulates Chemokine Production By Fibroblast-like Synoviocytes from Patients with Rheumtoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/stimulation-with-resistin-upregulates-chemokine-production-by-fibroblast-like-synoviocytes-from-patients-with-rheumtoid-arthritis/. Accessed .

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