M1 macrophage polarization is induced through Notch, JNK and ERK1/2 signaling activation, leading to increased release of inflammatory molecules, including TNF-α, IL-1β, IL-6 and IL-23 in the development of RA [27]; meanwhile, M2 macrophages exert anti-inflammatory effects by releasing IL-10 and transforming growth factor-β (TGF-β) in RA [28]. Here, MAPK8 is linked to rheumatoid arthritis.