Roflumilast prevents lymphotoxin α (TNF-ß)-induced inflammation activation and degradation of type 2 collagen in chondrocytes.
Inflamm Res
; 69(12): 1191-1199, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-32990777
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-ß (TNF-ß)-induced inflammation activation and degradation of type 2 collagen in chondrocytes.METHODS:
TNF-ß 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-ß stimulation, which were all inhibited by Roflumilast. Roflumilast suppressed the promoted iNOS expression and NO production induced by TNF-ß. MMP-3 and MMP-13 were up-regulated, and type 2 collagen was down-regulated by TNF-ß 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-ß.CONCLUSION:
Roflumilast may prevent TNF-ß-induced inflammation activation and degradation of type 2 collagen in chondrocytes.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Benzamidas
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Linfotoxina-alfa
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Condrocitos
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Colágeno Tipo II
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Inhibidores de Fosfodiesterasa 4
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Aminopiridinas
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Inflamación
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article