C-terminal truncation of IFN-γ\gamma inhibits proinflammatory macrophage responses and is deficient in autoimmune disease

International audienceControlled macrophage differentiation and activation in the initiation and resolution of inflammation is crucial for averting progression to chronic inflammatory and autoimmune diseases. Here we show a negative feedback mechanism for proinflammatory IFN-$\gamma$ activation of macrophages driven by macrophage-associated matrix metalloproteinase 12 (MMP12). Through C-terminal truncation of IFN-$\gamma$ at 135Glu↓Leu136 the IFN-$\gamma$ receptor-binding site was efficiently removed thereby reducing JAK-STAT1 signaling and IFN-$\gamma$ activation of proinflammatory macrophages. In acute peritonitis this signature was absent in Mmp12$^{–/–}$ mice and recapitulated in Mmp12$^{+/+}$ mice treated with a MMP12-specific inhibitor. Similarly, loss-of-MMP12 increases IFN-$\gamma$–dependent proinflammatory markers and iNOS$^+$/MHC class II$^+$ macrophage accumulation with worse lymphadenopathy, arthritic synovitis and lupus glomerulonephritis. In active human systemic lupus erythematosus, MMP12 levels were lower and IFN-$\gamma$ higher compared to treated patients or healthy individuals. Hence, macrophage proteolytic truncation of IFN-$\gamma$ attenuates classical activation of macrophages as a prelude for resolving inflammation

Synthesis, spectroscopic properties, crystal structures, antioxidant activities and enzyme inhibition determination of Co(II) and Fe(II) complexes of Schiff base

Considering the importance of metal complexes in the development of medical science, two different Schiff base Fe(II) and Co(II) metal complex compounds were synthesized with Schiff base obtained through the condensation of 1-(4-aminophenyl)ethanone with 2-hydroxy-3-methoxybenzaldehyde. The reactions of the ligand with Co(II) and Fe(II) metal ions enabled six coordination compounds with octahedral geometries. The novel metal complexes were characterized by IR, elemental analyses, magnetic susceptibility, mass spectra, UV-Vis, thermogravimetry-differential thermal analysis (TGA-DTA) and X-ray diffraction analysis. The antioxidant properties of the new compounds were investigated using different in vitro assays. Moreover, enzyme inhibition of derivatives complexes against carbonic anhydrase I and II isoenzymes (CA I and II) and acetylcholinesterase (AChE) was evaluated. The best inhibitor complex for CA I and II isoenzymes was the Fe(II) complex with K-i values of 52.83 +/- 11.52 and 63.34 +/- 8.88, respectively