Selective Inhibitors of the Inducible Nitric Oxide Synthase as Modulators of Cell Responses in LPS-Stimulated Human Monocytes

被引：12

作者：

Gallorini, Marialucia ^{[1
]}

Rapino, Monica ^{[2
]}

Schweikl, Helmut ^{[3
]}

Cataldi, Amelia ^{[1
]}

Amoroso, Rosa ^{[1
]}

Maccallini, Cristina ^{[1
]}

机构：

[1] Univ G dAnnunzio, Dept Pharm, Via Vestini 31, I-66100 Chieti, Italy

[2] Univ G dAnnunzio, Unit Chieti, CNR, Genet Mol Inst, Via Vestini 31, I-66100 Chieti, Italy

[3] Univ Hosp Regensburg, Dept Conservat Dent & Periodontol, D-93042 Regensburg, Germany

来源：

MOLECULES | 2021年 / 26卷 / 15期

关键词：

immunomodulation; inflammation; inhibitors; monocytes; nitric oxide; CYTOKINE PRODUCTION; INOS; DIFFERENTIATION; INFLAMMATION; MACROPHAGES;

D O I：

10.3390/molecules26154419

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Inducible nitric oxide synthase (iNOS) is a crucial enzyme involved in monocyte cell response towards inflammation, and it is responsible for the production of sustained amounts of nitric oxide. This free radical molecule is involved in the defense against pathogens; nevertheless, its continuous and dysregulated production contributes to the development of several pathological conditions, including inflammatory and autoimmune diseases. In the present study, we investigated the effects of two new iNOS inhibitors, i.e., 4-(ethanimidoylamino)-N-(4-fluorophenyl)benzamide hydrobromide (FAB1020) and N-{3-[(ethanimidoylamino)methyl]benzyl}-l-prolinamidedihydrochloride (CM554), on human LPS-stimulated monocytes, using the 1400 W compound as a comparison. Our results show that CM544 and FAB1020 are selective and decrease cytotoxicity, IL-6 secretion and LPS-stimulated monocyte migration. Furthermore, the modulation of iNOS, nitrotyrosine and Nrf2 were analyzed at the protein level. Based on the collected preliminary results, the promising therapeutic value of the investigated compounds emerges, as they appear able to modulate the pro-inflammatory LPS-stimulated response in the low micromolar range in human monocytes.

引用

页数：12

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