Dexamethasone attenuates oxidation of extracellular matrix proteins by human monocytes.
In response to infection or in immune complex-mediated diseases, inflammatory cells may oxidatively damage extracellular matrix (ECM) proteins. In this study we evaluated whether human monocytes could oxidize ECM and whether this could be modulated by exposure to LPS, IgG complexes, and dexamethasone (DEX). Wells in tissue culture plates were coated with the ECM preparation Matrigel. Porous inserts with or without the human monocyte cell line THP-1 were placed into ECM-containing wells and cells were exposed to control conditions or to LPS (10 ng/ml), IgG complexes (200 and 500 microg/ml), or DEX (10(-7) and 10(-6) M). ECM was then subjected to Western blot analysis using an antibody to oxidized protein. In addition, Western blot analysis was carried out on DEX-treated cells to evaluate expression of the NADPH oxidase components p67-phox and gp91-phox. THP-1 cells enhanced ECM oxidation and this effect was augmented by LPS and by IgG aggregates. Preincubation of cells with DEX attenuated ECM oxidation and was also associated with decreased expression of p67-phox and gp91-phox. These findings suggest that human monocytes can oxidize ECM proteins and that this may be modulated by IgG complexes and LPS. Dexamethasone appears to attenuate ECM oxidation and a better understanding of this mechanism might allow for interventions to minimize oxidative damage to ECM proteins by monocytes in infectious and inflammatory states.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen; D003907:Dexamethasone / Q000494:pharmacology*; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007797:Laminin; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D010750:Phosphoproteins / Q000378:metabolism; D011509:Proteoglycans
D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D007074:Immunoglobulin G; D007797:Laminin; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D011509:Proteoglycans; C079789:neutrophil cytosol factor 67K; C059485:matrigel; D003907:Dexamethasone; D003094:Collagen; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases