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To further investigate the molecular mechanisms governing these processes, we sought to describe the role of phospholipase A<jats:sub>2<\/jats:sub>(PLA<jats:sub>2<\/jats:sub>) in Mtb\u2010induced ROS generation and inflammatory mediator release by microglia. Inhibition of secretory PLA<jats:sub>2<\/jats:sub>(sPLA<jats:sub>2<\/jats:sub>), but not cytosolic PLA<jats:sub>2<\/jats:sub>(cPLA<jats:sub>2<\/jats:sub>), profoundly abrogated Mtb\u2010mediated ROS release, the generation of various inflammatory mediators (tumor necrosis factor, interleukin\u20106, cyclooxygenase\u20102, inducible nitric oxide synthase, and matrix metalloproteinase\u20102 and \u22129), and the activation of nuclear factor (NF)\u2010\u03baB and MAPKs (ERK1\/2, p38, and JNK\/SAPK) by murine microglial BV\u20102 cells or primary mixed glial cells. Interruption of the Ras\/Raf\u20101\/MEK1\/ERK1\/2 pathway abolished Mtb\u2010induced sPLA<jats:sub>2<\/jats:sub>activity, whereas the blockage of JNK\/SAPK or p38 activity had no effect. Specific inhibition of sPLA<jats:sub>2<\/jats:sub>, but not cPLA<jats:sub>2<\/jats:sub>, suppressed the upregulation of ERK1\/2 phosphorylation by Mtb stimulation, suggesting the existence of a mutual dependency between the ERK1\/2 and sPLA<jats:sub>2<\/jats:sub>pathways. Moreover, examination of the protein kinase C (PKC) family revealed that classical PKCs are involved in Mtb\u2010induced sPLA<jats:sub>2<\/jats:sub>activation by microglia. Taken together, our results demonstrate for the first time that sPLA<jats:sub>2<\/jats:sub>, either through pathways comprising Ras\/Raf\u20101\/MEK1\/ERK1\/2 or the classical PKC family, plays an essential role in Mtb\u2010mediated ROS generation and inflammatory mediator release by microglial cells. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20832","type":"journal-article","created":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T19:45:13Z","timestamp":1230752713000},"page":"1091-1103","source":"Crossref","is-referenced-by-count":15,"title":["Secretory phospholipase A<sub>2<\/sub>plays an essential role in microglial inflammatory responses to<i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1002","volume":"57","author":[{"given":"Chul\u2010Su","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Min","family":"Yuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Min","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junghee","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung 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