Proinflammatory Effects of IL-1β Combined with IL-17A Promoted Cartilage Degradation and Suppressed Genes Associated with Cartilage Matrix Synthesis In Vitro

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 20; p. 3682
• Main Authors: Kongdang, Patiwat, Chokchaitaweesuk, Chatchadawalai, Tangyuenyong, Siriwan, Ongchai, Siriwan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.10.2019; MDPI
• Subjects: Animals; Arthritis; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Cartilage; Cartilage, Articular - growth & development; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; cartilage-specific anabolic gene; Cell adhesion & migration; Cell culture; Cells, Cultured; Chondrocytes - metabolism; Chondrocytes - pathology; Chondrogenesis - genetics; Collagen; Collagenase 3; cytokine combination; Cytokines; Degradation; Gene expression; Gene Expression Regulation; Genes; Glycosaminoglycans - genetics; Glycosaminoglycans - metabolism; Humans; IL-1β; Inflammation; Inflammation - genetics; Inflammation - pathology; inflammatory arthritis; Interleukin-17 - genetics; Interleukin-1beta - genetics; Matrix Metalloproteinase 13 - genetics; Metabolism; porcine cartilage explant model; porcine pellet culture model; proinflammatory cytokine; Proteoglycans - genetics; Sarcoma; Swine; Synovial sarcoma; Tissue inhibitor of metalloproteinase 1; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-TNF; cartilage-specific anabolic gene; proinflammatory cytokine; porcine cartilage explant model; porcine pellet culture model; cytokine combination; inflammatory arthritis
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24203682

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.