title: N-[3-(aminomethyl)benzyl]acetamidine (1400 W) as a potential immunomodulatory agent.
abstract: This study was designed to investigate the relationship between NO, IL-12, and TNF-α production by J774A.1 macrophages activated with LPS and IFN-γ in the presence of N-[3-(aminomethyl)benzyl]acetamidine (1400 W). 1400 W is a novel, highly selective inhibitor of inducible nitric oxide synthase (iNOS). We compared the obtained data with the effect of N(G)-monomethyl-L-arginine (L-NMMA) (a nonselective NOS inhibitor) and L-N(G)-(1-iminoethyl)lysine (L-NIL) (a relatively selective inhibitor of iNOS activity) on cells in this model. To investigate the involvement of an exogenous NO on IL-12 and TNF-α production we used NO donor-S-nitrosocaptopril (S-NO-Cap). The most potent inhibitor of NO generation was 1400 W. This compound also markedly increased IL-12 p40 secretion and decreased TNF-α release. L-NIL suppressed both NO and TNF-α production, but it did not change IL-12 p40 synthesis. The effect of L-NMMA on NO generation was weaker than other inhibitors. Moreover, it decreased TNF-α secretion slightly but not significantly. IL-12 p40 production by stimulated cells was inhibited by S-NO-Cap in a dose dependent manner, but no effect on TNF-α release was observed. The potency and selectivity of 1400 W as an inhibitor of iNOS and cytokine release modifier are encouraging for therapeutic use.
authors.affiliation: Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41 808 Zabrze, Poland.
authors.forename: Anna
authors.identifier: 0000-0003-0796-8818
authors.initials: A
authors.lastname: Mertas
authors.affiliation: Regional Centre of Blood Donation and Blood Treatment in Opole, Kośnego 55, 45 372 Opole, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Duliban
authors.affiliation: Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41 808 Zabrze, Poland.
authors.forename: Ewelina
authors.identifier: 0000-0001-8114-2112
authors.initials: E
authors.lastname: Szliszka
authors.affiliation: Department of Orthodontics, Medical University of Silesia in Katowice, Plac Traugutta 2, 41 800 Zabrze, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Machorowska-Pieniążek
authors.affiliation: Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41 808 Zabrze, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Król
mesh_terms: D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007097:Imines / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D018664:Interleukin-12 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004791:Enzyme Inhibitors; D007097:Imines; D007155:Immunologic Factors; C496401:N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; C060039:S-nitrosocaptopril; D018664:Interleukin-12; D002216:Captopril; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase