Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In the presence of genotoxic stress poly(ADP-ribose) polymerase-1 (PARP-1) leads to NAD(+) and ATP depletion, participating in the pathogenesis of several disorders including inflammation. Accordingly, chemical inhibitors of PARP-1 are efficacious anti-inflammatories, albeit the underlying molecular mechanisms are still under debate. 2. This study investigated the effect of the PARP-1 inhibitors 6(5H)-phenanthridinone and benzamide as well as that of benzoic acid, an inactive analogue of benzamide, on development of experimental allergic encephalomyelitis (EAE) in rats. Both 6(5H)-phenanthridinone and benzamide attenuated development of EAE, reducing clinical score, neuroimmune infiltration and expression of inflammatory mediators such as inducible nitric oxide synthase, interleukin-1beta and -2, cyclooxygenase-2, tumour necrosis factor-alpha and interferon-gamma in the spinal cord of myelin-immunized rats. Importantly, no evidence of NAD(+) and ATP depletion as well as poly(ADP-ribose) formation was detected in the spinal cord. 3. By contrast, a robust formation of poly(ADP-ribose) occurred in B- and T-cell areas in lymph nodes of myelin-immunized rats and was suppressed by the treatment with 6(5H)-phenanthridinone and benzamide. In cultures of activated rat lymphocytes, 6(5H)-phenanthridinone and benzamide reduced the DNA-binding activity of NF-kappaB and AP-1 and transcription of pro-inflammatory cytokines such as interleukin-2, interferon-gamma and tumour necrosis factor-alpha. 4. Notably, benzoic acid did not reproduce the in vivo and in vitro effects of its parent compound. 5. These findings indicate that PARP-1 promotes transcriptional activation in lymphocytes and inhibitors of its enzymatic activity are useful for the treatment of autoimmune disorders of the central nervous system.
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PMID:Inhibitors of poly(ADP-ribose) polymerase-1 suppress transcriptional activation in lymphocytes and ameliorate autoimmune encephalomyelitis in rats. 1241 6

Peroxisome proliferator-activated receptor-gamma is a nuclear receptor transcription factor that regulates cell growth, differentiation and homeostasis. PPARgamma agonists have been used in the treatment of obesity, diabetes, cancer and inflammation. We and others have shown recently that PPARgamma agonists ameliorate experimental allergic encephalomyelitis (EAE), a Th1 cell-mediated autoimmune disease model of multiple sclerosis (MS). We have further shown that PPARgamma agonists inhibit EAE through blocking IL-12 signaling leading to Th1 differentiation and the PPARgamma-deficient heterozygous mice (PPARgamma(+/-)) develop an exacerbated EAE. In this study, we show that in vivo treatment (i.p.) with 100 mug PPARgamma antagonists, Bisphenol A diglycidyl ether (BADGE) or 2-Chloro-5-nitro-N-(4-pyridyl)benzamide (T0070907), on every other day from day 0 to 30, increased the severity and duration of EAE in C57BL/6 wild-type and PPARgamma(+/-) mice. The exacerbation of EAE by PPARgamma antagonists associates with an augmented neural antigen-induced T cell proliferation, IFNgamma production or Th1 differentiation. These results further suggest that PPARgamma is a critical physiological regulator of CNS inflammation and demyelination in EAE.
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PMID:PPARgamma antagonists exacerbate neural antigen-specific Th1 response and experimental allergic encephalomyelitis. 1609 Dec 93

Peroxisome proliferator-activated receptor-gamma is a nuclear receptor transcription factor that regulates cell growth, differentiation and homeostasis. PPARgamma agonists have been used to treat obesity, diabetes, cancer and inflammation and recent studies have shown the protective effects of PPARgamma agonists on experimental allergic encephalomyelitis (EAE), a Th1 cell-mediated autoimmune disease model of multiple sclerosis (MS). Our studies have further demonstrated that the PPARgamma agonists, 15d-PGJ2 and Ciglitazone, inhibit EAE through blocking IL-12 signaling leading to Th1 differentiation and the PPARgamma deficient heterozygous mice (PPARgamma+/-) or those treated with PPARgamma antagonists develop an exacerbated EAE in association with an augmented Th1 response. In this study, we show that the PPARgamma antagonists, Bisphenol A diglycidyl ether (BADGE) and 2-chloro-5-nitro-N-(4-pyridyl)benzamide (T0070907), reverse the inhibition of EAE by the PPARgamma agonists, Ciglitazone and 15-Deoxy-Delta(12,14)-Prostaglandin J2, in C57BL/6 wild-type and PPARgamma+/- mice. The reversal of EAE by BADGE and T0070907 was associated with restoration of neural antigen-induced T cell proliferation, IFNgamma production and Th1 differentiation inhibited by Ciglitazone and 15d-PGJ2. These results suggest that Ciglitazone and 15d-PGJ2 ameliorate EAE through PPARgamma-dependent mechanisms and further confirm a physiological role for PPARgamma in the regulation of CNS inflammation and demyelination in EAE.
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PMID:PPARgamma antagonists reverse the inhibition of neural antigen-specific Th1 response and experimental allergic encephalomyelitis by Ciglitazone and 15-deoxy-Delta12,14-prostaglandin J2. 1684 32