The contribution of nitric oxide and interferon gamma to the regulation of the neuro-inflammation in experimental autoimmune encephalomyelitis

Willenborg, David O.; Staykova, Maria; Fordham, Sue; O’Brien, Nikki C.; Liñares, David

doi:10.1016/j.jneuroim.2007.09.007

Cited by 63 publications

(47 citation statements)

References 78 publications

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“…Immunostimulatory CD11b + Gr-1 + cells cross-prime Ag-specific T cells in vitro and in vivo Cross-priming is an important function of DCs (5) that has also been reported for neutrophils (7). We therefore tested whether ID8 tumor-induced immunostimulatory CD11b + Gr-1 + cells could cross-prime T cells.…”

Section: Cell Proliferationmentioning

confidence: 89%

“…In addition to expressing an array of adhesion molecules, neutrophils can also respond to a wide variety of stimuli through surface receptors for diverse molecules, such as cytokines, complement, adenosine, the Fc portion of Abs, and TLRs (6). Neutrophils are recruited to the site of infection, phagocytose pathogens, and destroy them by releasing reactive oxygen species and NO (7)(8)(9). In addition to their intracellular granules containing large amounts of peroxidases and proteases, neutrophils can also secrete cytokines and chemokines.…”

mentioning

confidence: 99%

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Antigen-Specific Immunity and Cross-Priming by Epithelial Ovarian Carcinoma-Induced CD11b+Gr-1+ Cells

Tomihara

Guo

Shin

et al. 2010

The Journal of Immunology

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Both innate and adaptive immune systems are considered important for cancer prevention, immunosurveillance, and control of cancer progression. It is known that, although both systems initially eliminate emerging tumor cells efficiently, tumors eventually escape immune attack by a variety of mechanisms, including differentiation and recruitment of immunosuppressive CD11b+Gr-1+ myeloid suppressor cells into the tumor microenvironment. However, we show that CD11b+Gr-1+ cells found in ascites of epithelial ovarian cancer-bearing mice at advanced stages of disease are immunostimulatory rather than being immunosuppressive. These cells consist of a homogenous population of cells that morphologically resemble neutrophils. Moreover, like dendritic cells, immunostimulatory CD11b+Gr-1+ cells can strongly cross-prime, augmenting the proliferation of functional CTLs via signaling through the expression of costimulatory molecule CD80. Adoptive transfer of these immunostimulatory CD11b+Gr-1+ cells from ascites of ovarian cancer-bearing mice results in the significant regression of s.c. tumors even without being pulsed with exogenous tumor Ag prior to adoptive transfer. We now show for the first time that adaptive immune responses against cancer can be augmented by these cancer-induced granulocyte-like immunostimulatory myeloid (CD11b+Gr-1+) cells, thereby mediating highly effective antitumor immunity in an adoptive transfer model of immunity.

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Section: Cell Proliferationmentioning

confidence: 89%

mentioning

confidence: 99%

Antigen-Specific Immunity and Cross-Priming by Epithelial Ovarian Carcinoma-Induced CD11b+Gr-1+ Cells

Tomihara

Guo

Shin

et al. 2010

The Journal of Immunology

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“…The inflammatory phase includes the synthesis of NO and TNF-a by activated macrophages. In the CNS, NO can act during the onset of the disease as a tissue-damaging free radical (2), and TNF-a can initiate a myelin-directed immune response (3). The partial reduction of NO (4) and TNF-a (5) synthesis prevents the development of EAE.…”

mentioning

confidence: 99%

Ceramide Synthase 6 Plays a Critical Role in the Development of Experimental Autoimmune Encephalomyelitis

Schiffmann

Ferreiròs

Birod

et al. 2012

The Journal of Immunology

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Ceramides are mediators of apoptosis and inflammatory processes. In an animal model of multiple sclerosis (MS), the experimental autoimmune encephalomyelitis (EAE) model, we observed a significant elevation of C16:0-Cer in the lumbar spinal cord of EAE mice. This was caused by a transiently increased expression of ceramide synthase (CerS) 6 in monocytes/macrophages and astroglia. Notably, this corresponds to the clinical finding that C16:0-Cer levels were increased 1.9-fold in cerebrospinal fluid of MS patients. NO and TNF-α secreted by IFN-γ–activated macrophages play an essential role in the development of MS. In murine peritoneal and mouse-derived RAW 264.7 macrophages, IFN-γ–mediated expression of inducible NO synthase (iNOS)/TNF-α and NO/TNF-α release depends on upregulation of CerS6/C16:0-Cer. Downregulation of CerS6 by RNA interference or endogenous upregulation of C16:0-Cer mediated by palmitic acid in RAW 264.7 macrophages led to a significant reduction or increase in NO/TNF-α release, respectively. EAE/IFN-γ knockout mice showed a significant delay in disease onset accompanied by a significantly less pronounced increase in CerS6/C16:0-Cer, iNOS, and TNF-α compared with EAE/wild-type mice. Treatment of EAE mice with l-cycloserine prevented the increase in C16:0-Cer and iNOS/TNF-α expression and caused a remission of the disease. In conclusion, CerS6 plays a critical role in the onset of MS, most likely by regulating NO and TNF-α synthesis. CerS6 may represent a new target for the inhibition of inflammatory processes promoting MS development.

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“…Although there is an increased understanding as to the physiological and pathological properties of nitric oxide in health and disease, the role of NO in the pathogenesis of MS is still not well defined (Encinas et al, 2005;Willenborg et al, 2007). The sources of NO, the amount and sites of NO production, and the molecules NO reacts with might contribute to the great variability of the disease promoting or suppressing effects in MS.…”

mentioning

confidence: 99%

Distinct role of nitric oxide and peroxynitrite in mediating oligodendrocyte toxicity in culture and in experimental autoimmune encephalomyelitis

Vana

Ribeiro

et al. 2011

Neuroscience

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The contribution of nitric oxide and interferon gamma to the regulation of the neuro-inflammation in experimental autoimmune encephalomyelitis

Cited by 63 publications

References 78 publications

Antigen-Specific Immunity and Cross-Priming by Epithelial Ovarian Carcinoma-Induced CD11b+Gr-1+ Cells

Antigen-Specific Immunity and Cross-Priming by Epithelial Ovarian Carcinoma-Induced CD11b+Gr-1+ Cells

Ceramide Synthase 6 Plays a Critical Role in the Development of Experimental Autoimmune Encephalomyelitis

Distinct role of nitric oxide and peroxynitrite in mediating oligodendrocyte toxicity in culture and in experimental autoimmune encephalomyelitis

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