(A) Fra-1 mRNA expression in peripheral blood cells of patients with RA at different levels of inflammatory disease activity measured by DAS28. DAS28 of less than 2.6 indicated low/no disease activity (n = 11), more than 2.7 and less than 5.1 indicated moderate disease activity (n = 11), and more than 5.2 indicated high disease activity (n = 12). (B) Correlation between mRNA expression of Fra-1 and Arg1 (left) or arginase activity (right) in peripheral blood cells or serum, respectively. Rel exp, relative expression. (C) Immunofluorescence image for CD68 (magenta), Fra-1 (green), Arg1 (red), and DAPI (blue) in joint sections from RA patients in remission (DAS28 = 1.81) and moderate/high disease activity (DAS28 = 4.01). Scale bars: 100 μm. Arrowheads point to CD68+ macrophages. White inset boxes are 3 times magnified from the original magnification. (D) CD68+ cells were quantified for their Fra-1/Arg1 ratio by the mean gray value in the synovial tissue of RA patients (n = 14) in remission (DAS28 < 2.6, n = 9) or moderate/high disease activity (DAS28>3.2, n = 5). Each point represents the ratio of the mean gray value (Fra-1/Arg1) per macrophage. (E) Schematic of Fra-1 actions in macrophages: Fra-1 blocks antiinflammatory responses in macrophages by the inhibition of the Arg1 pathways. *P < 0.05; **P < 0.01.