Heme oxygenase-1 inhibits macrophage proinflammatory activity. (A) Peritoneal macrophages from HO-1+/+, HO-1+/−, and HO-1+/+ mice were cultured in the presence or absence of oxLDL 50 μg/ml for 6 h. IL-6 and MCP-1 were determined by ELISA. *p < 0.001 as compared with controls. Data taken from Orozco et al. (2007). (B) HO-1 expression varies in different subtypes of macrophages. Upon monocyte differentiation into macrophages, they can polarize into one of the five proposed subtypes, M1, M2, M4, Mox, and Mhem. Each subtype is induced by specific stimuli as shown along the arrows that derive from the macrophage Mø atop, and characterized by a set of phenotypic markers and/or gene expression shown below each one of them. While some of macrophage subtypes are proposed to simulate atherogenesis such as M1 and M4, others are proposed to inhibit lesion development such as M2 and Mhem. Mox macrophages, generated after treatment with oxPAPC, are dependent on Nrf2 with a role in atherogenesis still to be determined.