Down-regulatory effect of N-chlorotaurine on tryptophan degradation and neopterin production in human PBMC.
N-Chlorotaurine (NCT) plays an important role in the human defense system as a main component of long-lived oxidants, and shows bactericidal, fungicidal, and virucidal activity. Besides this role, NCT seems to act regulatory on immunocompetent cells by altering cytokine production. NCT inhibited nitric oxide, TNF-alpha, and prostaglandin E(2) (PGE(2)) production in activated rodent macrophages, and suppressed superoxide anion, IL-6, and IL-8 formation in human polymorphonuclear leukocytes. In this study, the influence of NCT on the production of neopterin and the activation of the enzyme indoleamine-2,3 dioxygenase (IDO) was investigated in human peripheral blood mononuclear cells (PBMC). Both events are well established to be triggered by IFN-gamma and therefore related to Th1-type immune activation. Mitogen-induced neopterin production as well as tryptophan degradation were drastically reduced upon addition of NCT. Results fit in the concept of a reduction of pro-inflammatory cytokines by this compound. In contrast to earlier results, where NCT was suggested to act primarily down-regulatory on Th2 cells, we propose also a strong suppressive effect of NCT on Th1-type immunity.
Wirleitner
Barbara
B
Institute of Medical Chemistry and Biochemistry, Medical University of Innsbruck, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria.
Neurauter
Gabriele
G
Nagl
Markus
M
Fuchs
Dietmar
D
D002470:Cell Survival / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D019798:Neopterin / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D010835:Phytohemagglutinins; D003208:Concanavalin A; D013654:Taurine; D007737:Kynurenine; C043410:N-chlorotaurine; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase