NOS2 and injury: HMGB1 could induce M1 polarization via TLR2, TLR4, and RAGE/NF−κB signaling pathways, leading to LPS−induced acute lung injury (124), meanwhile, it significantly yielded the expression of the M1 marker inducible nitric oxide synthase (iNOS) while decreasing the M2 marker IL-10 in macrophages (137).