Group IB secretory phospholipase A2 stimulates CXC chemokine ligand 8 production via ERK and NF-kappa B in human neutrophils

• Published in: The Journal of immunology (1950) 2004-11, Vol.173 (10), p.6433-6439
• Main Authors: Jo, Eun Jin, Lee, Ha-Young, Lee, Youl-Nam, Kim, Jung Im, Kang, Hyun-Kyu, Park, Dae-Won, Baek, Suk-Hwan, Kwak, Jong-Young, Bae, Yoe-Sik
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium - physiology; Enzyme Activation - immunology; Extracellular Signal-Regulated MAP Kinases - physiology; Group IB Phospholipases A2; Humans; Interleukin-8 - biosynthesis; Interleukin-8 - genetics; Interleukin-8 - metabolism; Intracellular Fluid - metabolism; Intracellular Fluid - physiology; MAP Kinase Signaling System - physiology; Neutrophils - enzymology; Neutrophils - immunology; Neutrophils - metabolism; NF-kappa B - metabolism; NF-kappa B - physiology; Phospholipases A - metabolism; Phospholipases A - physiology; Phospholipases A2; Receptors, Chemokine - physiology; RNA, Messenger - biosynthesis; Swine; Transcription, Genetic - drug effects; Transcription, Genetic - immunology; Transcriptional Activation - drug effects; Transcriptional Activation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.10.6433

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.