5,6-Dihydroxyindole-2-carboxylic acid, a diffusible melanin precursor, is a potent stimulator of lipopolysaccharide-induced production of nitric oxide by J774 macrophages.
Pre-incubation of J774 murine macrophages with 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a diffusible intermediate in the biosynthesis of eumelanins, leads to a marked increase in the levels of nitric oxide (NO) produced by lipopolysaccharide (LPS)-induced NO-synthase (iNOS). The effect varies with DHICA concentration being maximum at a concentration of 1 x 10(-6)M, and is suppressed by the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). No stimulation is observed when macrophages are exposed to DHICA after activation with LPS, indicating that the indole does not affect the catalytic activity of iNOS. These results point to a hitherto unrecognized role of DHICA as a chemical messenger mediating interaction between active melanocytes and macrophages in epidermal inflammatory and immune responses.
D'Acquisto
F
F
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Carnuccio
R
R
d'Ischia
M
M
Misuraca
G
G
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004058:Diffusion; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011498:Protein Precursors / Q000378:metabolism / Q000494:pharmacology; D012485:Salmonella typhi; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D007211:Indoles; D008070:Lipopolysaccharides; D008543:Melanins; D011498:Protein Precursors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C030692:5,6-dihydroxy-2-indolylcarboxylic acid; D001120:Arginine; D019001:Nitric Oxide Synthase