SSChighCD11bhighLy-6ChighLy-6Glow myeloid cells curtail CD4 T cell response by inducible nitric oxide synthase in murine hepatitis

2014 ◽  
Vol 54 ◽  
pp. 89-97 ◽  
Author(s):  
Kai Zhu ◽  
Na Zhang ◽  
Nining Guo ◽  
Juhao Yang ◽  
Jianrong Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cell ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Cell Response ◽  
Myeloid Cells ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals αβ T Cell Receptor-positive Cells and Interferon-γ, but not Inducible Nitric Oxide Synthase, Are Critical for Granuloma Necrosis in a Mouse Model of Mycobacteria-induced Pulmonary Immunopathology

2001 ◽  
Vol 194 (12) ◽  
pp. 1847-1859 ◽  
Author(s):  
Stefan Ehlers ◽  
Jochen Benini ◽  
Heinz-Dieter Held ◽  
Christiane Roeck ◽  
Gottfried Alber ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cell ◽  
Nitric Oxide Synthase ◽  
T Cell Receptor ◽  
Inducible Nitric Oxide Synthase ◽  
Bacterial Load ◽  
Cell Receptor ◽  
Ifn Γ ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The immunological basis of tuberculin-induced necrosis, known for more than a century as “Koch's phenomenon,” remains poorly understood. Aerosol infection in mice with the highly virulent Mycobacterium avium strain TMC724 causes progressive pulmonary pathology strongly resembling caseating necrosis in human patients with tuberculosis. To identify the cellular and molecular mediators causing this pathology, we infected C57BL/6 mice and mice selectively deficient in recombinase activating gene (RAG)-1, αβ T cell receptor (TCR), γδ TCR, CD4, CD8, β2-microglobulin, interferon (IFN)-γ, interleukin (IL)-10, IL-12p35, IL-12p35/p40, or iNOS with M. avium by aerosol and compared bacterial multiplication, histopathology, and respiratory physiology in these mice. The bacterial load in the lung was similarly high in all mouse groups. Pulmonary compliance, as a surrogate marker for granulomatous infiltrations in the lung, deteriorated to a similar extent in all groups of mice, except in αβ TCR-knockout (KO) and IL-12–KO mice in which compliance was higher, and in IFN-γ and inducible nitric oxide synthase–KO mice in which compliance was reduced faster. Progressive caseation of pulmonary granulomas never occurred in αβ TCR-KO, IL-12–KO, and IFN-γ–KO mice and was reduced in CD4-KO mice. In summary, αβ TCR+ cells and IFN-γ are essential for the development of mycobacteria-induced pulmonary caseous necrosis. In contrast, high mycobacterial load and extensive granulomatous infiltration per se are not sufficient to cause caseation, nor is granuloma necrosis linked to the induction of nitric oxide.

scholarly journals Inducible Nitric Oxide Synthase Deficiency in Myeloid Cells Does Not Prevent Diet-Induced Insulin Resistance

2010 ◽  
Vol 24 (7) ◽  
pp. 1413-1422 ◽  
Author(s):  
Min Lu ◽  
PingPing Li ◽  
Jan Pferdekamper ◽  
WuQiang Fan ◽  
Maziyar Saberi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Myeloid Cells ◽  
Mixed Effect ◽  
Insulin Resistant ◽  
Oxide Synthase ◽  
Inos Inhibition ◽  
Inducible Nitric Oxide

Abstract Recent findings denote an important contribution of macrophage inflammatory pathways in causing obesity-related insulin resistance. Inducible nitric oxide synthase (iNOS) is activated in proinflammatory macrophages and modestly elevated in insulin-responsive tissues. Although the benefits of systemic iNOS inhibition in insulin-resistant models have been demonstrated, the role of macrophage iNOS in metabolic disorders is not clear. In the current work, we used bone marrow transplantation (BMT) to generate mice with myeloid iNOS deficiency [iNOS BMT knockout (KO)]. Interestingly, disruption of iNOS in myeloid cells did not protect mice from high-fat diet-induced obesity and insulin resistance. When mice were treated with the iNOS inhibitor, N6-(1-Iminoethyl)-L-lysine hydrochloride (L-NIL), we observed a significant and comparable improvement of glucose homeostasis and insulin sensitivity in both wild-type and iNOS BMT KO mice. We further demonstrated that absence of iNOS in primary macrophages did not affect acute TLR4 signaling pathways and had only a modest and mixed effect on inflammatory gene expression. With respect to TNFα treatment, iNOS KO macrophages showed, if anything, a greater inflammatory response. In summary, we conclude that iNOS inhibition in tissues other than myeloid cells is responsible for the beneficial effects in obesity/insulin resistance.

scholarly journals Inducible nitric oxide synthase in T cells regulates T cell death and immune memory

2004 ◽  
Vol 113 (12) ◽  
pp. 1734-1742 ◽  
Author(s):  
Monika Vig ◽  
Smita Srivastava ◽  
Usha Kandpal ◽  
Hadassah Sade ◽  
Virginia Lewis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Immune Memory ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Estrogen Up-Regulates Inducible Nitric Oxide Synthase, Nitric Oxide, and Cyclooxygenase-2 in Splenocytes Activated with T Cell Stimulants: Role of Interferon-γ

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 662-671 ◽  
Author(s):  
Ebru Karpuzoglu ◽  
Jillian B. Fenaux ◽  
Rebecca A. Phillips ◽  
Andrea J. Lengi ◽  
François Elvinger ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cell ◽  
Nitric Oxide Synthase ◽  
Autoimmune Diseases ◽  
Inducible Nitric Oxide Synthase ◽  
Cyclooxygenase 2 ◽  
Con A ◽  
Inos Protein ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Estrogen is implicated in many autoimmune diseases and is a robust immunomodulator. For example, it regulates interferon (IFN)-γ, a cytokine believed to up-regulate inducible nitric oxide synthase (iNOS). A notable gap in the literature is a lack of information on the regulation of nitric oxide in immune tissues by estrogen. We now show that activation of splenocytes with T cell stimulants [concanavalin-A (Con-A) or anti-CD3 antibodies] results in copious release of nitric oxide in splenocyte cultures from estrogen-treated but not placebo-treated mice. Moreover, even a low dose of T cell stimulants induced nitric oxide in splenocytes from estrogen-treated, but not placebo-treated, mice. Con-A-activated splenocytes from estrogen-treated mice also have up-regulated iNOS mRNA, iNOS protein, and cyclooxygenase-2 (a nitric oxide-regulated downstream proinflammatory protein) when compared with controls. Our studies suggest that the induction of nitric oxide by activated splenocytes from estrogen-treated mice is mediated in part by IFNγ. First, blocking costimulatory signals mediated through interactions of CD28 and B7 molecules by CTLA-4Ig markedly decreased not only IFNγ but also nitric oxide. Second, estrogen treatment of IFNγ-knockout (IFNγ−/−) mice did not induce iNOS protein or nitric oxide. Finally, in vitro addition of recombinant IFNγ to Con-A-activated splenocytes from IFNγ(−/−) mice induced iNOS protein primarily in estrogen-treated mice. Overall, this is the first report to show that estrogen treatment up-regulates IFNγ-inducible-iNOS gene expression, iNOS protein, nitric oxide, and cyclooxygenase-2 as an indirect consequence of activation of T cells. These findings may have wide implications to immunity and inflammatory disorders including female-predominant autoimmune diseases.

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