title: Src-mediated regulation of inflammatory responses by actin polymerization.
abstract: Although the role of the actin cytoskeleton has become increasingly elucidated, the role of actin polymerization in inflammatory processes remains poorly understood. Here, we examine the role of the actin cytoskeleton during LPS-mediated inflammatory events in RAW264.7 cells and peritoneal macrophages. We observed that actin cytoskeleton disruption by cytochalasin B and siRNA to cytoplasmic actin strongly down-regulated LPS-mediated inflammatory responses such as NO production, PGE(2) release, and TNF-alpha secretion. Actin cytoskeleton disruption by cytochalasin B down-regulated a series of signaling cascades including PI3K, Akt, and IKK, but not MAPKs, necessary for NF-kappaB activation without down-regulating total forms of the proteins as assessed by measuring their phosphorylation levels. In particular, cytochalasin B significantly inhibited LPS-induced both phosphorylation and kinase activity of Src without altering total level, implying that Src may be a potential pharmacological target of actin cytoskeleton rearrangement. Moreover, the direct association of Src with actin was actin polymerization-dependent according to immunoprecipitation analysis performed with a GFP-actin wild type and HA-tagged Src. Therefore, our data suggest that actin cytoskeleton rearrangement may be a key event during the regulation of inflammatory responses that modulates the activity of Src and its downstream signaling molecules.
authors.affiliation: School of Bioscience and Biotechnology, Institute of Bioscience and Biotechnology, Kangwon National University, 192-1 Hyoja-2-Dong, Chuncheon 200-701, Republic of Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Yong Gyu
authors.initials: YG
authors.lastname: Lee
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Byeon
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
authors.forename: Jongsun
authors.initials: J
authors.lastname: Park
authors.forename: David R
authors.initials: DR
authors.lastname: Katz
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Chain
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000199:Actins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D018836:Inflammation Mediators / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011108:Polymers / Q000378:metabolism* / Q000494:pharmacology; D019061:src-Family Kinases / Q000502:physiology*
chemical_list: D000199:Actins; D018836:Inflammation Mediators; D011108:Polymers; D003571:Cytochalasin B; D019061:src-Family Kinases