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• W2772575461 abstract "Osteoarthritis (OA) is a low-grade chronic inflammatory joint disease. Innate immunity contributes to OA progression, mediated by TLR2 and TLR4. We evaluated the role of cluster determinant 44 (CD44), a transmembrane glycoprotein, in regulating TLR2-linked macrophage activation and resultant proinflammatory responses. TLR2 stimulation was performed on differentiated THP-1 macrophages in the presence or absence of a CD44-specific Ab or hyaluronan (HA). NF-κB nuclear translocation, IL-1 β and TNF-α gene expression, and protein concentrations were determined. Anti-CD44 Ab and HA treatments reduced NF-κB translocation, IL-1β and TNF-α expression, and production (p < 0.001). Inhibition of proinflammatory response in macrophages by HA was mediated by CD44. Protein phosphatase 2A mediated the reduction in NF-κB translocation by HA. CD44 knockdown reduced NF-κB nuclear translocation and downstream IL-1β and TNF-α protein production following TLR2 receptor stimulation (p < 0.001). CD44+/+ murine bone marrow-derived macrophages produced higher TNF-α compared with CD44-/- macrophages following TLR2 stimulation (p < 0.01). HA dose-dependently inhibited TLR2-induced TNF-α production by murine bone marrow-derived macrophages (p < 0.001). OA synovial fluids (SF) stimulated TLR2 and TLR4 receptors and induced NF-κB translocation in THP-1 macrophages. Anti-CD44 Ab treatment significantly reduced macrophage activation by OA SF (p < 0.01). CD44 regulated TLR2 responses in human macrophages, whereby a reduction in CD44 levels or engagement of CD44 by its ligand (HA) or a CD44-specific Ab reduced NF-κB translocation and downstream proinflammatory cytokine production. A CD44-specific Ab reduced macrophage activation by OA SF, and CD44 is a potentially novel target in OA treatment." @default.
• W2772575461 created "2017-12-22" @default.
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• W2772575461 date "2017-12-01" @default.
• W2772575461 modified "2023-10-14" @default.
• W2772575461 title "Role of CD44 in Regulating TLR2 Activation of Human Macrophages and Downstream Expression of Proinflammatory Cytokines" @default.
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• W2772575461 doi "https://doi.org/10.4049/jimmunol.1700713" @default.
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