Theiler's virus infection induces the expression of cyclooxygenase-2 in murine astrocytes: inhibition by the anti-inflammatory cytokines interleukin-4 and interleukin-10.
Theiler's murine encephalomyelitis virus (TMEV) causes an acute encephalomyelitis followed by a persistent infection of the central nervous system (CNS) resulting in a chronic inflammation and axonal demyelination in susceptible strains of mice. The pathogenesis of TMEV-induced demyelinating disease remains unknown, but infection of brain glial cells is a critical factor for virus persistence in the CNS. In the present study we investigated the effects of the anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) on the production of inflammatory mediators, such as prostaglandins, after infection of primary astroglial SJL/J murine cultures with TMEV. This infection resulted in a time-dependent transcription of the gene encoding cyclooxygenase-2 (COX-2) and an increased production of prostaglandin E2 (PGE(2)). Both, IL-4 but mainly, IL-10 (1 and 10 ng/ml) decreased the TMEV-induced expression of COX-2 as well as the synthesis of PGE(2). Interestingly, treatment with IL-10 completely abrogated COX-2 induction. The molecular mechanisms involved in the regulation of COX-2 expression by TMEV are unknown, but the effects of anti-inflammatory cytokines may involve the inhibition of the transcription factor nuclear factor B activity and lead to strategies capable of interrupting the inflammatory cascade triggered by TMEV in brain glial cells.
Molina-Holgado
Eduardo
E
Instituto Cajal, Departamento de Plasticidad Neural, Consejo Superior de Investigaciones Científicas, Avenida Dr Arce 37, 28002 Madrid, Spain.
Arévalo-Martín
Angel
A
Ortiz
Sergio
S
Vela
José M
JM
Guaza
Carmen
C
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D006224:Cricetinae; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004679:Encephalomyelitis / Q000188:drug therapy / Q000201:enzymology* / Q000821:virology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism* / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics; D053701:Receptors, Interleukin-10; D017945:Theilovirus / Q000472:pathogenicity*
D007527:Isoenzymes; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D015847:Interleukin-4; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone