N-[3-(aminomethyl)benzyl]acetamidine (1400 W) as a potential immunomodulatory agent.

Anna Mertas, Hanna Duliban, Ewelina Szliszka, Agnieszka Machorowska-Pieniążek, Wojciech Król
Author Information
  1. Anna Mertas: Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41 808 Zabrze, Poland. ORCID
  2. Hanna Duliban: Regional Centre of Blood Donation and Blood Treatment in Opole, Kośnego 55, 45 372 Opole, Poland.
  3. Ewelina Szliszka: Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41 808 Zabrze, Poland. ORCID
  4. Agnieszka Machorowska-Pieniążek: Department of Orthodontics, Medical University of Silesia in Katowice, Plac Traugutta 2, 41 800 Zabrze, Poland.
  5. Wojciech Król: Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41 808 Zabrze, Poland.

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.

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MeSH Term

Animals
Captopril
Cell Line
Enzyme Inhibitors
Imines
Immunologic Factors
Interleukin-12
L-Lactate Dehydrogenase
Macrophage Activation
Macrophages
Mice
Nitric Oxide Synthase
Nitrites
Tumor Necrosis Factor-alpha

Chemicals

Enzyme Inhibitors
Imines
Immunologic Factors
N-((3-(aminomethyl)phenyl)methyl)ethanimidamide
Nitrites
Tumor Necrosis Factor-alpha
S-nitrosocaptopril
Interleukin-12
Captopril
L-Lactate Dehydrogenase
Nitric Oxide Synthase

Word Cloud

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