Baricitinib Inhibits Proinflammatoly Cytokine Production, Proliferation and Cell Migration in Human Lung Fibroblasts

Takeo Isozaki¹, Rei Takahashi², Kohei Maeda², Toshihiro Tanioka², Kunika Shimizu³, Kazutaka Kawamori³, Noriko Konishi⁴, Shinichiro Nishimi³, Sho Ishii³, Kuninobu Wakabayashi³ and Tsuyoshi Kasama³, ¹Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan, ²Division of Pathogenesis and Translational Medicine, Department of Clinical Pharmacy, Showa University School of Pharmacy, Tokyo, Japan, ³Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Japan, ⁴Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan

Meeting: ACR Convergence 2022

Keywords: Adhesion, Adhesion molecules, cytokines, Fibroblasts, Other, interstitial lung disease, rheumatoid arthritis

Session Information

Date: Sunday, November 13, 2022

Title: Cytokines and Cell Trafficking Poster

Session Type: Poster Session B

Session Time: 9:00AM-10:30AM

Background/Purpose: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction. Baricitinib is a selective small molecule inhibitor of JAK 1 and 2 enzymes, and is currently in clinical development for the treatment of RA. However, a direct role of baricitinib for interstitial lung disease has not been demonstrated. Here, we examined baricitinib inhibited human lung fibroblast (HLF) proliferation, migration and proinflammatoly cytokine production.

Methods: To determine if the JAK-STAT enzyme was expressed in HLFs, we performed immunohistochemistry. In order to confirm that baricitinib inhibited STAT signaling phosphorylation, interleukin (IL)-6 and IL-6 receptor (IL-6R) stimulated HLFs was used for western blotting. To determine whether baricitinib was involved in proinflammatoly cytokine production, VEGF, ICAM-1, fractalkine/CX3CL1, CXCL16, ENA-78/CXCL5, IL-8/CXCL8, MCP-1/CCL2 and RANTES/CCL5 in baricitinib treated HLF conditioned medium was measured using enzyme-linked immunosorbent assay (ELISA). Finally, to confirm if HLF proliferation and migration was inhibited with baricitinib, HLF chemotaxis assay and proliferation assay were performed.

Results: JAK1, 2 and 3 was expressed in HLFs. We found that phosphorylated STAT1, STAT3 and STAT5 signaling in IL-6 and IL-6R stimulated baricitinib treated HLFs was significantly decreased at 10 minutes compared to nontreated HLFs. VEGF in baricitinib treated HLF conditioned medium was significantly decreased compared with in nontreated HLF conditioned medium (20.4 ± 0.4 pg/ml and 56.3 ± 0.6 pg/ml, p< 0.05, respectively). MCP-1/CCL2 in in baricitinib treated HLF conditioned medium was also significantly decreased compared with in nontreated HLF conditioned medium (110.1 ± 1.6 pg/ml and 870.7 ± 12.2 pg/ml, p< 0.05, respectively). Additionally, we found that baricitinib suppressed HLF migration compared nontreated HLF. Finally, we also found that baricitinib treated HLF has showed less proliferation in response to IL-6 and IL-6R at 24 hours.

Conclusion: Baricitinib inhibited proinflammatory cytokine production and HLF migration and proliferation. These data indicate that baricitinib acts in lung fibrosis, suggesting that baricitinib prevent interstitial lung disease.

Disclosures: T. Isozaki, None; R. Takahashi, None; K. Maeda, None; T. Tanioka, None; K. Shimizu, None; K. Kawamori, None; N. Konishi, None; S. Nishimi, None; S. Ishii, None; K. Wakabayashi, None; T. Kasama, None.

To cite this abstract in AMA style:

Isozaki T, Takahashi R, Maeda K, Tanioka T, Shimizu K, Kawamori K, Konishi N, Nishimi S, Ishii S, Wakabayashi K, Kasama T. Baricitinib Inhibits Proinflammatoly Cytokine Production, Proliferation and Cell Migration in Human Lung Fibroblasts [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/baricitinib-inhibits-proinflammatoly-cytokine-production-proliferation-and-cell-migration-in-human-lung-fibroblasts/. Accessed .

« Back to ACR Convergence 2022

ACR Meeting Abstracts - https://acrabstracts.org/abstract/baricitinib-inhibits-proinflammatoly-cytokine-production-proliferation-and-cell-migration-in-human-lung-fibroblasts/