TNF and rheumatoid arthritis: By downregulation of Ras/Raf/ERK and PTEN/PI3K/AKT signaling, Spry2 overexpression suppressed AKT and ERK pathways and production of proinflammatory cytokines IL-1β, IL-6, matrix metalloproteinase (MMP)-1, and MMP-3 and effectively inhibited the hyperproliferation induced by TNF-α in RA FLSs [29].