TNF and rheumatoid arthritis: Macrophage-produced PGE2 is a response to IL-17 of T cells, which negatively regulates the expression of TNF-α and IL-17, as well as the TNF-α/IL-1-mediated activation of FLS via EP2 and EP4 receptors, resulting in the modulation of proinflammatory cascades in RA (60).