Akademik Veri Yönetim Sistemi
Canadian Journal of Physiology and Pharmacology, cilt.99, sa.4, ss.418-426, 2021 (SCI-Expanded)
It has been clearly indicated that osteoarthritis (OA) is an inflammatory and degenerative disease that could be promoted by Rho-kinase (ROCK); however, little is known about the role of ROCK/inhibitor jB alpha (IjB-a)/nuclear factor-jB (NF-jB) p65 pathway activation in interleukin-1b (IL-1b) induced inflammatory response and oxidative stress in primary human chondrocytes. To test this hypothesis, we focused on determining ROCK-II, IjB-a, p-IjB-a, NF-jB p65, p-NF-jB p65, IL-6, tumor necrosis factor alpha (TNF-a), cyclooxygenase-2 (COX-2), p22phox, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subtype 4 (NOX4) protein expression, ROCK-II activity, NADPH oxidase levels, and total antioxidant capacity (TAC) in the presence and absence of ROCK-inhibitor fasudil. IL-1b (2 ngmL-1, 24 h) increased the expression of ROCK-II, p-IjB-a, NF-jB p65, p-NF-jB p65, IL-6, TNF-a, COX-2, and p22phox proteins, and decreased the expression of IjB-a, and the NOX4 protein level did not alter. ROCK activity and NADPH oxidase levels were increased, whereas the TAC was decreased by IL-1b. Fasudil (105-107 M) reversed all these changes induced by IL-1b. These results demonstrate that ROCK/IjB-a/NF-jB p65 pathway activation contributes to the IL-1b-induced inflammatory response and oxidative stress, and thus, ROCK inhibition might be a beneficial treatment option for OA patients mainly based on its anti-inflammatory and antioxidant effects.