{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:06:54Z","timestamp":1790251614256,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,11,1]],"date-time":"2005-11-01T00:00:00Z","timestamp":1130803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Viral infection is one of the leading causes of brain encephalitis and meningitis. Recently, it was reported that Toll\u2010like receptor\u20103 (TLR3) induces a double\u2010stranded RNA (dsRNA)\u2010mediated inflammatory signal in the cells of the innate immune system, and studies suggested that dsRNA may induce inflammation in the central nervous system (CNS) by activating the CNS\u2010resident glial cells. To explore further the connection between dsRNA and inflammation in the CNS, we have studied the effects of dsRNA stimulation in astrocytes. Our results show that the injection of polyinosinic\u2010polycytidylic acid (poly(I:C)), a synthetic dsRNA, into the striatum of the mouse brain induces the activation of astrocytes and the expression of TNF\u2010\u03b1, IFN\u2010\u03b2, and IP\u201010. Stimulation with poly(I:C) also induces the expression of these proinflammatory genes in primary astrocytes and in CRT\u2010MG, a human astrocyte cell line. Furthermore, our studies on the intracellular signaling pathways reveal that poly(I:C) stimulation activates I\u03baB kinase (IKK), extracellular signal\u2010regulated kinase (ERK), and c\u2010Jun N\u2010terminal kinase (JNK) in CRT\u2010MG. Pharmacological inhibitors of nuclear factor\u2010\u03baB (NF\u2010\u03baB), JNK, ERK, glycogen synthase kinase\u20103\u03b2 (GSK\u20103\u03b2), and dsRNA\u2010activated protein kinase (PKR) inhibit the expression of IL\u20108 and IP\u201010 in astrocytes, indicating that the activation of these signaling molecules is required for the TLR3\u2010mediated chemokine gene induction. Interestingly, the inhibition of PI3 kinase suppressed the expression of IP\u201010, but upregulated the expression of IL\u20108, suggesting differential roles for PI3 kinase, depending on the target genes. These data suggest that the TLR3 expressed on astrocytes may initiate an inflammatory response upon viral infection in the CNS. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20278","type":"journal-article","created":{"date-parts":[[2005,11,1]],"date-time":"2005-11-01T17:16:53Z","timestamp":1130865413000},"page":"248-256","source":"Crossref","is-referenced-by-count":132,"title":["TLR3\u2010mediated signal induces proinflammatory cytokine and chemokine gene expression in astrocytes: Differential signaling mechanisms of TLR3\u2010induced IP\u201010 and IL\u20108 gene 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Bae","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungpyo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joong Soo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung 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