title: PDT-induced HSP70 externalization up-regulates NO production via TLR2 signal pathway in macrophages.
abstract: We studied the molecular mechanism underlying PDT-induced apoptosis-dependent macrophage activation, particularly through NO production. We demonstrate that NO production is initially induced by HSP70 on the apoptotic cell surface, and is further enhanced by macrophage phagocytosis. Additionally, we found that apoptotic cells, through TLR2, could activate PI3K, and this could be either dependent or independent of the activation of MyD88. These results reveal a novel pathway linking innate immune signalling to apoptotic cells and point at HSP70 as an important antitumor immunostimulant. They also indicate that PDT-induced apoptosis has an important role in macrophage innate immunity.
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Song
authors.forename: Feifan
authors.initials: F
authors.lastname: Zhou
authors.forename: Wei R
authors.initials: WR
authors.lastname: Chen
authors.forename: Da
authors.initials: D
authors.lastname: Xing
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007113:Immunity, Innate; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010778:Photochemotherapy; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018840:HSP70 Heat-Shock Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019869:Phosphatidylinositol 3-Kinases