Interleukin-17F Down-Regulates the Plasminogen/Plasmin Pathway in Chondrocytes

Shihoko Tanigawa, Takayuki Kawato, Yukiko Aida, Naoto Suzuki, Kuniyasu Ochiai, Hideo Matsumura, Masao Maeno
2011 Journal of Hard Tissue Biology  
Interleukin-17 (IL-17) is a proinflammatory cytokine involved in autoimmune diseases such as rheumatoid arthritis (RA). IL-17 consists of six ligands that signal through five receptors (IL-17Rs). Serine proteinases, such as plasmin and plasminogen activators (PAs), as well as matrix metalloproteinases (MMPs) degrade the extracellular matrix during cartilage remodeling.In contrast, plasminogen activator inhibitor-1 (PAI-1), an endogenous inhibitor of PAs, forms a complex with PA to inhibit
more » ... n production. In the present study, we examined the effect of IL-17F on the plasminogen/plasmin pathway in cartilage using human articular chondrocytes. We evaluated the effects of IL-17F on the expression of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), PAI-1, and cyclooxygenases (COXs), as well as on the production of prostaglandin E 2 (PGE 2 ). We also examined the indirect effects of PGE 2 on the above IL-17F-induced/ reduced components using NS-398, a specific inhibitor of COX-2 activity. Cells were cultured with or without IL-17F in the presence or absence of NS-398 for up to 28 days. mRNA and protein expression levels of PAs, PAI-1, and COXs were determined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. PGE 2 production was determined by ELISA. The addition of IL-17F increased the expression of PAI-1 and COX-2, as well as the production of PGE 2 , whereas uPA and COX-1 expression decreased and tPA expression was unaffected. NS-398 did not block the reducing/stimulating effects of IL-17F on the expression of COX-1 and COX-2. In contrast, NS-398 may be, in part, responsible for IL-17F-induced/reduced uPA and PAI-1 expression. Our results suggest that IL-17F suppresses the plasminogen/ plasmin pathway by increasing PAI-1 expression and decreasing uPA expression in chondrocytes.
doi:10.2485/jhtb.20.195 fatcat:dcp6dce6tbdqxevwkfaaqoapiu