The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18 (J Neurosci, 2010, 30(57):15811-15820)

報告日期: 2011/03/22
報告時間: 17:10/18:00
報告學生: 吳佩樺
講評老師: 林秋烽
附件下載:

Full text: http://basicmed.med.ncku.edu.tw/admin/up_img/000322-1.pdf

 The Inflammasome Sensor, NLRP3, Regulates CNS Inflammation and Demyelination via Caspase-1 and Interleukin-18

Jha, S., et al. The Journal of Neuroscience 30(47):15811–15820 (2010)
 
Speaker: Suky Peihua Wu (吳佩樺)
Commentator: Dr. Chiou-Feng Lin (林秋烽)
Time: 17:00-18:00, Mar 22, 2011
Place: Room 602
 
Abstract:
NLRP3 (NLR family, Pyrin-domain containing 3) is the key component of a caspase-1-activating inflammasome complex, which is composed of the adaptor ASC (apoptotic speck-containing protein with a card) and procaspase-1 (1). Activation of caspase 1 promotes the maturation of proinflammatory cytokines, such as IL-1β and IL-18 (1). Recently, patients with cryopyrin-associated periodic syndromes (CAPS), an autoinflammatory syndrome induced by autosomal dominant mutations in NLRP3 and characterized by hyperactivation of the inflammasome as well as increased IL-1β, exhibit neurological lesions and corpus callosum demyelination (2). These reports suggest a role of NLRP3 in CNS inflammation and demyelination. Here, the authors applied a cuprizone-induced demyelination mouse model to investigate the role of NLRP3 in CNS. Nlrp3 expression and IL-1β production were increased in the corpus callosum after 3 weeks of cuprizone treatment. The disease symptoms in the cuprizone model, such as recruitment of microglia and astrocytes, demyelination, and oligodendrocyte loss in the corpus callosum, were reduced in mice lacking the Nlrp3 gene during 3 to 4 weeks post cuprizone treatment. Attenuated disease progression and demyelination in Nlrp3-/- mice were also found in the experimental autoimmune encephalomyelitis model, which mimics multiple sclerosis in human. In addition to NLRP3, caspase 1- and IL-18-deficient mice also showed attenuated disease symptoms, whereas IL-1β-deficient mice exhibited no difference in disease progression compared to wildtype control. During the remyelination stage, there was no difference in myelin staining and mature oligodendrocyte repopulation in Nlrp3-/- relative to wildtype control. Surprisingly, IL-18-deficient mice exhibited a faster remyelination as measured by myelin staining. In conclusion, this study provides a potential role of NLRP3, caspase 1, and IL-18 in amplifying CNS inflammation and demyelination.
 
Reference:
1. J. Tschopp, K. Schroder, Nat Rev Immunol 10, 210 (Mar).
2. S. Compeyrot-Lacassagne, T. A. Tran, S. Guillaume-Czitrom, I. Marie, I. Kone-Paut, Rheumatology (Oxford) 48, 1618 (Dec, 2009).