title: Group IB secretory phospholipase A2 stimulates CXC chemokine ligand 8 production via ERK and NF-kappa B in human neutrophils.
abstract: Although the level of group IB secretory phospholipase A(2) (sPLA(2)-IB) has been reported to be up-regulated during inflammatory response, the role of sPLA(2)-IB on the regulation of inflammation and immune responses has not been fully elucidated. In this study, we found that sPLA(2)-IB stimulates the expression and secretion of CXCL8 without affecting other proinflammatory cytokines, such as IL-1beta or TNF alpha in human neutrophils. The induction of CXCL8 secretion by sPLA(2)-IB occurs at both the transcription and translational levels and correlates with activation of NF-kappaB. Moreover, the NF-kappaB inhibitors pyrrolidinedithiocarbamate, dexamethasone, or sulfasalazine were found to prevent CXCL8 production by sPLA(2)-IB in human neutrophils. In addition, the signaling events induced by sPLA(2)-IB included activation of the MAPK ERK and an increase in intracellular Ca(2+), which are both required for CXCL8 production. The exogenous addition of sPLA(2)-IB did not induce arachidonic acid release from human neutrophils, and the inactivation of sPLA(2)-IB by EGTA did not affect CXCL8 production by sPLA(2)-IB in human neutrophils. Taken together, we suggest that sPLA(2)-IB plays a role in the modulation of inflammatory and immune responses via the sPLA(2) receptor, by inducing CXCL8 in human neutrophils.
authors.affiliation: Medical Research Center for Cancer Molecular Therapy and Dong-A University, Busan 602-714, Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Jo
authors.forename: Ha-Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Youl-Nam
authors.initials: YN
authors.lastname: Lee
authors.forename: Jung Im
authors.initials: JI
authors.lastname: Kim
authors.forename: Hyun-Kyu
authors.initials: HK
authors.lastname: Kang
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Park
authors.forename: Suk-Hwan
authors.initials: SH
authors.lastname: Baek
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Kwak
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D004789:Enzyme Activation / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D054500:Group IB Phospholipases A2; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism / Q000502:physiology*; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000502:physiology; D013552:Swine; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D015533:Transcriptional Activation / Q000187:drug effects / Q000276:immunology
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D048049:Extracellular Signal-Regulated MAP Kinases; D010741:Phospholipases A; D054500:Group IB Phospholipases A2; C516202:PLA2G1B protein, human; D054467:Phospholipases A2; D002118:Calcium