title: Anti-inflammatory activities of phospholipase C inhibitor U73122: Inhibition of monocyte-to-macrophage transformation and LPS-induced pro-inflammatory cytokine expression.
abstract: A wide range of biological processes are controlled by phospholipase C (PLC)/Ca(2+) signaling, which could be blocked by PLC-specific inhibitor U73122. Whether inhibition of PLC with chemical inhibitor U73122 affects the inflammatory response in monocytes/macrophages is currently unknown. In this study, we demonstrated that U73122 inhibited PMA-induced in vitro differentiation of human promonocytic U937 cells into macrophages as reflected by the reduction of cell adherence and the decreased expression of macrophage specific marker CD163. It is possible that U73122 blocked PMA-induced adhesion of U937 cells partially by down regulation and inactivation of both Pyk2 and paxillin signaling. Furthermore, the expression of LPS-induced pro-inflammatory cytokines TNF-α and IL-1β was significantly blocked by U73122 in both dU937 cells and mouse primary peritoneal macrophages. These results suggest that PLC is involved in the sophisticated inflammatory response by monocytes/macrophages, and thereby chemical antagonists of PLC may be potential agents for the suppression of inflammatory response.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, 48 Wenhui East Road, Yangzhou 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 48 Wenhui East Road, Yangzhou 225009, China.
authors.forename: Liqian
authors.initials: L
authors.lastname: Zhu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, 48 Wenhui East Road, Yangzhou 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 48 Wenhui East Road, Yangzhou 225009, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yuan
authors.affiliation: College of Veterinary Medicine, Yangzhou University, 48 Wenhui East Road, Yangzhou 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 48 Wenhui East Road, Yangzhou 225009, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: College of Veterinary Medicine, Yangzhou University, 48 Wenhui East Road, Yangzhou 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 48 Wenhui East Road, Yangzhou 225009, China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Ding
authors.affiliation: College of Veterinary Medicine, Yangzhou University, 48 Wenhui East Road, Yangzhou 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 48 Wenhui East Road, Yangzhou 225009, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhu
authors.affiliation: The State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 1 Xujiaping, Chengguan District, Lanzhou 730046, Gansu, China. Electronic address: zhuqiyun@caas.cn.
authors.forename: Qiyun
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology*; D051418:Focal Adhesion Kinase 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000502:physiology*; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D004963:Estrenes; D008070:Lipopolysaccharides; C496061:PXN protein, human; D051419:Paxillin; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D051418:Focal Adhesion Kinase 2
keywords: Phospholipase C; Pro-inflammatory cytokines; Scavenger receptors; U73122