Abstract
Combinations of IL-1β and other proinflammatory cytokines reportedly promote the severity of arthritis. We aimed to investigate the effects of IL-1β combined with IL-17A on cartilage degradation and synthesis in in vitro models. Cartilage explant degradation was determined using sulfated glycosaminoglycans (S-GAGs) levels, matrix metalloproteinase (MMP13) gene expression, uronic acid, and collagen contents. Cell morphology and accumulation of proteoglycans were evaluated using hematoxylin-eosin and safranin O staining, respectively. In the pellet culture model, expressions of cartilage-specific anabolic and catabolic genes were evaluated using real-time qRT-PCR. Early induction of MMP13 gene expression was found concomitantly with significant S-GAGs release. During the prolonged period, S-GAGs release was significantly elevated, while MMP-13 enzyme levels were persistently increased together with the reduction of the cartilaginous matrix molecules. The pellet culture showed anabolic gene downregulation, while expression of the proinflammatory cytokines, mediators, and MMP13 genes were elevated. After cytokine removal, these effects were restored to nearly basal levels. This study provides evidence that IL-1β combined with IL-17A promoted chronic inflammatory arthritis by activating the catabolic processes accompanied with the suppression of cartilage anabolism. These suggest that further applications, which suppress inflammatory enhancers, especially IL-17A, should be considered as a target for arthritis research and therapy.
Highlights
Proinflammatory cytokines are critical factors involved in the pathogenesis of inflammatory arthritis, which triggers, amplifies, and prolongs the catabolic progression of joint diseases [1]
Significant changes in sulfated glycosaminoglycans (S-GAGs) release and the remaining uronic acid (UA) content were observed when 2 ng/mL of IL-1β was used in combination with IL-17A at concentrations of 4–8 ng/mL
Proinflammatory cytokines play significant roles in the pathogenesis of inflammatory arthritis and Proinflammatory cytokines play significant rolesshown in the that pathogenesis of inflammatory escalate the severity of joint inflammation
Summary
Proinflammatory cytokines are critical factors involved in the pathogenesis of inflammatory arthritis, which triggers, amplifies, and prolongs the catabolic progression of joint diseases [1]. IL-1β induces the production of cartilage-degrading enzymes, including matrix metalloproteinases (MMPs) and inhibits the synthesis of the cartilaginous extracellular matrix (ECM) in the chondrocytes [2]. IL-17A or IL-17 is involved in several chronic diseases, including rheumatoid arthritis (RA), and it upregulates other proinflammatory cytokines, including IL-1β and IL-6 [3]. IL-17-producing cells, that is, Th17 cells, are activated by IL-1β to produce IL-17, which induces the production of other proinflammatory cytokines, including IL-1β in the activation loop [4]. In the animal joint system, IL-17A induces the mRNA expression of MMPs and suppresses COL2A1 gene expression in the cartilage [5]
Sign-in/Register to view highlights & summary 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.
