Regulation of iNOS on Immune Cells and Its Role in Diseases

Xue, Qiao; Ying-chun, Yan; Zhang, Ruihua; Xiong, Huabao

doi:10.3390/ijms19123805

Cited by 309 publications

(222 citation statements)

References 75 publications

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“…Previous studies showed that iNOS sourced from macrophages regulates M1 macrophage differentiation and the production of inflammatory cytokines usually produced by M1 macrophages, but this finding is not fully understood. 39 Therefore, the high levels of CD11b þ /iNOS þ cells in the lungs of C. gattii-infected mice identified on d 7 may impair M1 macrophage differentiation and the production of pro-inflammatory cytokines, as verified on d 14 and 21 post infection ( Figure 6). The effect of iNOS expression on the regulation of M1 macrophages produces a significant increase in CD11b þ /Arg-1 þ cells in the pulmonary tissue of infected mice on d 14 and 21 post infection.…”

Section: Discussionmentioning

confidence: 76%

“…24,25 Thus, our findings suggest an important role of iNOS in the pathogenesis of C. gattii strain R265 that may be related to the maintenance of virulence, which may be supported by the 'division of labour' hypothesised by Voelz et al 25 or may be related to the effect of iNOS expression in the balance between M1 and M2 macrophages. 8,39 The current work indicates that the effect of inhibition and lack of iNOS on progression of C. gattii infection should be evaluated among distinct strains of mice.…”

Section: Discussionmentioning

confidence: 99%

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iNOS/Arginase-1 expression in the pulmonary tissue over time duringCryptococcus gattiiinfection

et al. 2019

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Inhalation of Cryptococcus gattii yeasts (causing cryptococcosis) triggers an anti-cryptococcal immune response initiated by macrophages, neutrophils or dendritic cells, and the iNOS expressed by various cells may regulate the function and differentiation of innate and adaptive immune cells. Here, we evaluated the effect of progression of C. gattii infection on the host innate immune response. C. gattii infection in BALB/c mice spreads to several organs by 21 d post infection. The numbers of neutrophils and lymphocytes in the peripheral blood of C. gattii–infected mice were remarkably altered on that day. The frequency of CD11b+ cells and cell concentrations of CD4+ and CD8+ T cells was significantly altered in the pulmonary tissue of infected mice. We found a higher frequency of CD11b+/iNOS+ cells in the lungs of infected mice, accompanied by an increase in frequency of CD11b+/Arginase-1+ cells over time. Moreover, the iNOS/Arginase-1 expression ratio in CD11b+ cells reached its lowest value at 21 d post infection. In addition, the cytokine micro-environment in infected lungs did not show a pro-inflammatory profile. Surprisingly, iNOS knock-out prolonged the survival of infected mice, while their pulmonary fungal burden was higher than that of infected WT mice. Thus, C. gattii infection alters the immune response in the pulmonary tissue, and iNOS expression may play a key role in infection progression.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

iNOS/Arginase-1 expression in the pulmonary tissue over time duringCryptococcus gattiiinfection

et al. 2019

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“…NO is produced by three types of NO synthase (NOS): endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) [39]. In the immune response, large amounts of NO are mainly produced by iNOS in response to cytokine stimulation [40]. In chronic inflammation, iNOS is thought to be involved in the formation of granulomatous lesions [41].…”

Section: Discussionmentioning

confidence: 99%

Ranunculus bulumei Methanol Extract Exerts Anti-Inflammatory Activity by Targeting Src/Syk in NF-κB Signaling

2020

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1) Background: Ranunculus bulumei is a flowering plant that belongs to the Ranunculus species. Several Ranunculus species, such as R. aquatilis and R. muricatus, have traditionally been used to treat fever and rheumatism throughout Asia, suggesting that plants belonging to the Ranunculus species may have anti-inflammatory effects. To our knowledge, the pharmacological activity of R. bulumei has not been reported. Therefore, in this study, we aim to assess the anti-inflammatory activity of a methanol extract that was derived from R. bulumei (Rb-ME) in macrophage-mediated inflammatory responses and to identify the molecular mechanism that underlies any anti-inflammatory action.(2) Methods: The anti-inflammatory efficacy of Rb-ME was evaluated while using in vitro and in vivo experiments. The RAW264.7 cells and peritoneal macrophages were stimulated by lipopolysaccharide (LPS). In addition, LPS-induced peritonitis and HCl/EtOH-triggered gastritis models were produced. A nitric oxide (NO) assay, real-time PCR, luciferase reporter gene assay, western blot analysis, plasmid overexpression strategy, and in vitro kinase assay were used to determine the molecular mechanisms and target molecules of Rb-ME. The phytochemical active ingredients of Rb-ME were also identified by high performance liquid chromatograph (HPLC). (3) Results: Rb-ME reduced the production of NO and mRNA expression of iNOS, COX-2, IL-1β, and IL-6 without cytotoxicity. The protein secretion of TNF-α and IL-6 was also decreased by Rb-ME. HPLC analysis indicates that quercetin, luteolin, and kaempferol are the main active ingredients in the anti-inflammatory efficacy of Rb-ME. Rb-ME also blocked MyD88-induced NF-κB promoter activity and nuclear translocation of NF-κB subunits (p65 and p50). Moreover, Rb-ME reduced the phosphorylation of IκBα, Akt, p85, Src, and Syk, which are NF-κB upstream signaling molecules in LPS-activated RAW264.7 cells. According to the in vitro kinase assay, Rb-ME directly inhibits Syk kinase activity. The oral administration of Rb-ME alleviated inflammatory responses and the levels of p-IκBα in mice with LPS-induced peritonitis and HCl/EtOH-induced gastritis. (4) Conclusions Rb-ME has anti-inflammatory capacity by suppressing NF-κB signaling and it has been found to target Src and Syk in the NF-κB pathway. Based on this efficacy, Rb-ME could be developed as an anti-inflammatory herbal medicine.

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“…A pegylated form of the catabolic enzyme Arg I (peg-Arg I) can enhance the growth of tumors in mice in a manner that correlates with increased MDSC numbers through general control of the nonrepressed-2 eIF2α kinase [41]. NO can react with superoxide to form PNT and then directly inhibit T cells by nitrifying TCR, thereby reducing the affinity of TCR for antigen-MHC complexes presented by cancer cells and blocking the migration of T cells by nitrating T cell-specific chemokines [42,43]. The two major subpopulations of MDSCs exploit different mechanisms to inhibit T cell proliferation.…”

Section: Metabolic Mechanismsmentioning

confidence: 99%

Myeloid-derived suppressor cells—new and exciting players in lung cancer

et al. 2020

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Lung cancer (LC) is the leading cause of cancer-related death worldwide due to its late diagnosis and poor outcomes. As has been found for other types of tumors, there is increasing evidence that myeloid-derived suppressor cells (MDSCs) play important roles in the promotion and progression of LC. Here, we briefly introduce the definition of MDSCs and their immunosuppressive functions. We next specifically discuss the multiple roles of MDSCs in the lung tumor microenvironment, including those in tumor growth and progression mediated by inhibiting antitumor immunity, and the associations of MDSCs with a poor prognosis and increased resistance to chemotherapy and immunotherapy. Finally, we also discuss preclinical and clinical treatment strategies targeting MDSCs, which may have the potential to enhance the efficacy of immunotherapy.

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Regulation of iNOS on Immune Cells and Its Role in Diseases

Cited by 309 publications

References 75 publications

iNOS/Arginase-1 expression in the pulmonary tissue over time duringCryptococcus gattiiinfection

iNOS/Arginase-1 expression in the pulmonary tissue over time duringCryptococcus gattiiinfection

Ranunculus bulumei Methanol Extract Exerts Anti-Inflammatory Activity by Targeting Src/Syk in NF-κB Signaling

Myeloid-derived suppressor cells—new and exciting players in lung cancer

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