scholarly journals Myeloid cell-derived inducible nitric oxide synthase suppresses M1 macrophage polarization

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Geming Lu ◽  
Ruihua Zhang ◽  
Shuo Geng ◽  
Liang Peng ◽  
Padmini Jayaraman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Macrophage Polarization ◽  
Myeloid Cell ◽  
M1 Macrophage ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Myeloid cell-specific deletion of inducible nitric oxide synthase protects against smoke-induced pulmonary hypertension in mice

2021 ◽  
pp. 2101153
Author(s):  
Marija Gredic ◽  
Cheng-Yu Wu ◽  
Stefan Hadzic ◽  
Oleg Pak ◽  
Rajkumar Savai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Vascular Remodelling ◽  
Oxide Synthase ◽  
Pulmonary Vascular Remodelling ◽  
Inducible Nitric Oxide

Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), associated with increased mortality and morbidity. Intriguingly, pulmonary vascular alterations have been suggested to drive emphysema development. We previously identified inducible nitric oxide synthase (iNOS) as an essential enzyme for development and reversal of smoke-induced PH and emphysema, and showed that iNOS expression in bone-marrow-derived cells drives pulmonary vascular remodelling, but not parenchymal destruction. In this study, we aimed to identify the iNOS-expressing cell type driving smoke-induced PH and to decipher pro-proliferative pathways involved.To address this question we used 1) myeloid cell-specific iNOS knockout mice in chronic smoke exposure, 2) co-cultures of macrophages and pulmonary artery smooth muscle cells (PASMC) to decipher underlying signalling pathways.Myeloid cell-specific iNOS knockout prevented smoke-induced PH but not emphysema in mice. Moreover, iNOS deletion in myeloid cells ameliorated the increase in expression of CD206, a marker of M2 polarisation, on interstitial macrophages. Importantly, the observed effects on lung macrophages were hypoxia-independent, as these mice developed hypoxia-induced PH. In vitro, smoke-induced PASMC proliferation in co-cultures with M2-polarised macrophages could be abolished by iNOS deletion in phagocytic cells, as well as by ERK inhibition in PASMC. Crucially, CD206-positive and iNOS-positive macrophages accumulated in proximity of remodelled vessels in the lungs of COPD patients, as shown by immunohistochemistry.In summary, our results demonstrate that iNOS deletion in myeloid cells confers protection against PH in smoke-exposed mice and provide evidence for an iNOS-dependent communication between M2-like macrophages and PASMC in underlying pulmonary vascular remodelling.

289: Roles of Inducible Nitric Oxide Synthase in Voiding Function and Bladder Pain During Experimental Cystitis

2006 ◽  
Vol 175 (4S) ◽  
pp. 96-96
Author(s):  
Masayoshi Nomura ◽  
Hisae Nishii ◽  
Masato Tsutsui ◽  
Naohiro Fujimoto ◽  
Tetsuro Matsumoto
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Voiding Function ◽  
Bladder Pain ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Search for Potential Inducible Nitric Oxide Synthase Inhibitors with Favorable ADMET Profiles for the Therapy of Helicobacter pylori Infections

2020 ◽  
Vol 19 (30) ◽  
pp. 2795-2804 ◽  
Author(s):  
Ricardo Pereira Rodrigues ◽  
Juliana Santa Ardisson ◽  
Rita de Cássia Ribeiro Gonçalves ◽  
Tiago Branquinho Oliveira ◽  
Vinicius Barreto da Silva ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Helicobacter Pylori ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Crucial Role ◽  
Chemical Space ◽  
Target Selection ◽  
Oxide Synthase ◽  
Inos Inhibition ◽  
Inducible Nitric Oxide

Background: Helicobacter pylori is a gram-negative bacterium related to chronic gastritis, peptic ulcer and gastric carcinoma. During its infection process, promotes excessive inflammatory response, increasing the release of reactive species and inducing the production of pro-inflammatory mediators. Inducible Nitric Oxide Synthase (iNOS) plays a crucial role in the gastric carcinogenesis process and a key mediator of inflammation and host defense systems, which is expressed in macrophages induced by inflammatory stimuli. In chronic diseases such as Helicobacter pylori infections, the overproduction of NO due to the prolonged induction of iNOS is of major concern. Objective: In this sense, the search for potential iNOS inhibitors is a valuable strategy in the overall process of Helicobacter pylori pathogeny. Method: In silico techniques were applied in the search of interesting compounds against Inducible Nitric Oxide Synthase enzyme in a chemical space of natural products and derivatives from the Analyticon Discovery databases. Results: The five compounds with the best iNOS inhibition profile were selected for activity and toxicity predictions. Compound 9 (CAS 88198-99-6) displayed significant potential for iNOS inhibition, forming hydrogen bonds with residues from the active site and an ionic interaction with heme. This compound also displayed good bioavailability and absence of toxicity/or from its probable metabolites. Conclusion: The top-ranked compounds from the virtual screening workflow show promising results regarding the iNOS inhibition profile. The results evidenced the importance of the ionic bonding during docking selection, playing a crucial role in binding and positioning during ligand-target selection for iNOS.

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