Peroxisome proliferator-activated receptor-gamma agonists inhibit experimental allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1 differentiation

Natarajan, Chandramohan; Bright, John J.

doi:10.1038/sj.gene.6363832

Cited by 206 publications

(170 citation statements)

References 61 publications

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“…Namely, we did not observe any alterations in IL-12 expression in brain abscesses with ciglitazone treatment, whereas others have reported that this compound is capable of reducing IL-12 levels during EAE (73). However, it is important to acknowledge several differences in the nature of inflammatory insults between these infectious (brain abscess) and noninfectious (i.e., EAE) disease models.…”

Section: Discussioncontrasting

confidence: 42%

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses

Kielian

Syed

Liu

et al. 2008

The Journal of Immunology

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Brain abscesses result from a pyogenic parenchymal infection commonly initiated by Gram-positive bacteria such as Staphylococcus aureus. Although the host immune response elicited following infection is essential for effective bacterial containment, this response also contributes to the significant loss of brain parenchyma by necrosis that may be reduced by modulating the inflammatory response. Ciglitazone, a PPAR-γ agonist with anti-inflammatory properties, was evaluated for its ability to influence the course of brain abscess development when treatment was initiated 3 days following infection. Interestingly, abscess-associated bacterial burdens were significantly lower following ciglitazone administration, which could be explained, in part, by the finding that ciglitazone enhanced S. aureus phagocytosis by microglia. In addition, ciglitazone attenuated the expression of select inflammatory mediators during brain abscess development including inducible NO synthase, TNF-α, IL-1β, CXCL2, and CCL3. Unexpectedly, ciglitazone also accelerated brain abscess encapsulation, which was typified by the heightened expression of fibronectin and α-smooth muscle actin-positive myofibroblasts. Collectively, through its ability to attenuate excessive inflammation and accelerate abscess encapsulation, ciglitazone may effectively sequester brain abscesses and limit bacterial dissemination.

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Section: Discussioncontrasting

confidence: 42%

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses

Kielian

Syed

Liu

et al. 2008

The Journal of Immunology

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“…Consistent with this theory, whole-body PPAR-␥ ϩ/Ϫ mice and immune cell-specific PPAR-␥ null mice are more susceptible to autoimmune and intestinal inflammatory diseases (34,37,42). Furthermore, PPAR-␥ activation by synthetic or natural agonists in an inflammatory setting limits the extent of tissue injury (10,11). Epithelial cells, macrophages, effector CD4 ϩ T cells, and Treg play an important role in the immunopathogenesis of IBD (39).…”

Section: Discussionmentioning

confidence: 89%

Peroxisome Proliferator-Activated Receptor γ Is Required for Regulatory CD4+ T Cell-Mediated Protection against Colitis

Hontecillas

Bassaganya‐Riera

2007

The Journal of Immunology

144

141

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Peroxisome proliferator-activated receptor (PPAR) γ activation has been implicated in the prevention of immunoinflammatory disorders; however, the mechanisms of regulation of effector and regulatory CD4+ T cell functions by endogenously activated PPAR-γ remain unclear. We have used PPAR-γ-deficient CD4+ T cells obtained from tissue-specific PPAR-γ null mice (i.e., PPAR-γ fl/fl; MMTV-Cre+) to investigate the role of endogenous PPAR-γ on regulatory T cell (Treg) and effector CD4+ T cell function. Overall, we show that the loss of PPAR-γ results in enhanced Ag-specific proliferation and overproduction of IFN-γ in response to IL-12. These findings correlate in vivo with enhanced susceptibility of tissue-specific PPAR-γ null mice to trinitrobenzene sulfonic acid-induced colitis. Furthermore, the transfer of purified PPAR-γ null CD4+ T cells into SCID recipients results in enteric disease. To test the assertion that the deficiency of PPAR-γ in Treg impairs their ability to prevent effector T cell-induced colitis, we performed cotransfer studies. These studies demonstrate that PPAR-γ-expressing, but not PPAR-γ null Treg, prevent colitis induced by transfer of naive CD4+ T cells into SCID recipients. In line with these findings, the production of IFN-γ by spleen and mesenteric lymph node-derived CD4+ T cells was down-regulated following transfer of PPAR-γ-expressing, but not PPAR-γ null, Treg. In conclusion, our data suggest that endogenous PPAR-γ activation represents a Treg intrinsic mechanism of down-regulation of effector CD4+ T cell function and prevention of colitis.

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“…However, some interesting evidence suggests that neurons also participate in the inflammatory response in the CNS. For examples, neurons can produce COX-2-derived prostanoids (Davis and Laroche 2003;Natarajan and Bright 2002;Pavlov and Tracey 2005), several cytokines such as IL-1b and IL-18 (de Rivero Vaccari et al 2008;Fann et al 2013;Zou and Crews 2012), complement and macrophage colony-stimulating factor (Du Yan et al 1997). Moreover, in the brain of AD individuals, an inflammation-induced enzyme named iNOS has been reported to be expressed by degenerating neurons (Heneka et al 2001;Lee et al 1999;Vodovotz et al 1996).…”

Section: Neuronmentioning

confidence: 99%

Inflammation in Alzheimer’s Disease and Molecular Genetics: Recent Update

Zhang

et al. 2015

Arch. Immunol. Ther. Exp.

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Alzheimer's disease (AD) is a complex agerelated neurodegenerative disorder of the central nervous system. Since the first description of AD in 1907, many hypotheses have been established to explain its causes. The inflammation theory is one of them. Pathological and biochemical studies of brains from AD individuals have provided solid evidence of the activation of inflammatory pathways. Furthermore, people with long-term medication of anti-inflammatory drugs have shown a reduced risk to develop the disease. After three decades of genetic study in AD, dozens of loci harboring genetic variants influencing inflammatory pathways in AD patients has been identified through genome-wide association studies (GWAS). The most well-known GWAS risk factor that is responsible for immune response and inflammation in AD development should be APOE e4 allele. However, a growing number of other GWAS risk AD candidate genes in inflammation have recently been discovered. In the present study, we try to review the inflammation in AD and immunity-associated GWAS risk genes like HLA-DRB5/DRB1, INPP5D, MEF2C, CR1, CLU and TREM2.

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Peroxisome proliferator-activated receptor-gamma agonists inhibit experimental allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1 differentiation

Cited by 206 publications

References 61 publications

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses

Peroxisome Proliferator-Activated Receptor γ Is Required for Regulatory CD4+ T Cell-Mediated Protection against Colitis

Inflammation in Alzheimer’s Disease and Molecular Genetics: Recent Update

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