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- Title
Roflumilast prevents lymphotoxin α (TNF-β)-induced inflammation activation and degradation of type 2 collagen in chondrocytes.
- Authors
Zhao, Jingtong; Duan, Lian; Wang, Renxiang; Liu, Yi; Jiang, Jinlan
- Abstract
Background and purpose: Osteoarthritis (OA) is a chronic disease accompanied by severe inflammation. The inflammation activation in the chondrocytes and the degradation of the extracellular matrix were reported to be involved in the progress of OA. Roflumilast is a selective PDE4 inhibitor used for treating chronic obstructive pulmonary disease (COPD) and exerts significant anti-inflammation effects. The present study aims to investigate the effects of Roflumilast on tumor necrosis factor-β (TNF-β)-induced inflammation activation and degradation of type 2 collagen in chondrocytes. Methods: TNF-β was used to establish the in-vitro inflammation model on ATDC5 chondrocytes. Quantitative real-time polymerase chain reaction (QRT-PCR) and western blot were used to determine the expression level of tumor necrosis factor receptor 2 (TNFR2), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase 3 (MMP-3), matrix metalloproteinase 13 (MMP-13), type 2 collagen and nuclear factor kappa B (NF-κB) p65. The release of prostaglandin E2 (PGE2), MMP-3, and MMP-13 were evaluated by ELISA. The production of NO was determined by DAF-FM DA staining and the function of the NF-κB promoter was evaluated by Luciferase activity assay. Results: TNFR2 and COX-2 were upregulated and the release of PGE2 was promoted by TNF-β stimulation, which were all inhibited by Roflumilast. Roflumilast suppressed the promoted iNOS expression and NO production induced by TNF-β. MMP-3 and MMP-13 were up-regulated, and type 2 collagen was down-regulated by TNF-β stimulation, which were all reversed by Roflumilast. Roflumilast inhibited the promoted releasing of Interleukin-8 (IL-8) and Interleukin-12 (IL-12), expression of up-regulated NF-κB, and activation of NF-κB transcriptional activity induced by TNF-β. Conclusion: Roflumilast may prevent TNF-β-induced inflammation activation and degradation of type 2 collagen in chondrocytes.
- Subjects
TUMOR necrosis factor receptors; NITRIC-oxide synthases; COLLAGEN; OBSTRUCTIVE lung diseases; EXTRACELLULAR matrix; NF-kappa B
- Publication
Inflammation Research, 2020, Vol 69, Issue 12, p1191
- ISSN
1023-3830
- Publication type
Article
- DOI
10.1007/s00011-020-01404-3