Group IB secretory phospholipase A2 stimulates CXC chemokine ligand 8 production via ERK and NF-kappa B in human neutrophils.
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.
Jo
Eun Jin
EJ
Medical Research Center for Cancer Molecular Therapy and Dong-A University, Busan 602-714, Korea.
Lee
Ha-Young
HY
Lee
Youl-Nam
YN
Kim
Jung Im
JI
Kang
Hyun-Kyu
HK
Park
Dae-Won
DW
Baek
Suk-Hwan
SH
Kwak
Jong-Young
JY
Bae
Yoe-Sik
YS
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
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