Abstract
Rat annulus fibrosus (AF) cells were activated with interleukin-1 (IL-1) with or without extracellular signal-regulated kinase (ERK) inhibition. Factors associated with the anabolic/catabolic balance of the disc were determined. To clarify the role of ERK pathway in AF cells response to IL-1. IL-1 plays an important role in intervertebral disc degeneration. ERK is an important inflammatory pathway that plays a crucial role in the expression of inflammatory and catabolic genes induced by IL-1 in chondrocytes. However, the role of the ERK pathway in AF cells response to IL-1 has not been fully investigated. Rat AF cells in monolayer culture were exposed to IL-1, with or without ERK inhibition; ribonucleic acid was isolated for real time polymerase chain reaction analysis of gene expression, conditioned media analyzed for nitrite, prostaglandin E-2, and IL-6, Western blot was performed to detect the changes of protein expression. ERK specific inhibitor U0126 significantly inhibited IL-1-induced ERK activation. IL-1-dependent upregulation of iNOS, IL-6, Cox-2, (MMP)-3, and MMP-13 was significantly reduced by ERK inhibition. The decreased gene expression of collagen I, collagen II, collagen IX, and IGF-1 induced by IL-1 was also reversed by U0126. Gene expression of ADAMTS-4, ADAMTS-5, and TGF-b were not affected by IL-1 or ERK inhibition. IL-1 moderately upregulated aggrecan and TIMP-1 expression, ERK inhibition had no significant effect on aggrecan expression but decreased TIMP-1 expression in the presence of IL-1. ERK inhibition reversed the changes of protein expression of MMP-3, MMP-13, TIMP-1, aggrecan and collagen II induced by IL-1. IL-1-induced nitric oxide, prostaglandin E-2, and IL-6 accumulation were also reduced by ERK inhibition. These results suggest that IL-1 induces an imbalance between anabolic and catabolic events in AF cells, ERK inhibition could provide some protection against the adverse effects of IL-1. N/A.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
