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

Although the level of group IB secretory phospholipase A₂ (sPLA₂-IB) has been reported to be up-regulated during inflammatory response, the role of SPLA₂-IB on the regulation of inflammation and immune responses has not been fully elucidated. In this study, we found that SPLA₂-IB stimulates the expression and secretion of CXCL8 without affecting other proiniammatory cytokines, such as IL-1β or TNF α in human neutrophils. The induction of CXCL8 secretion by SPLA₂-IB occurs at both the transcription and translational levels and correlates with activation of NF-κB. Moreover, the NF-κB inhibitors pyrrolidinedithiocarbamate, dexamethasone, or sulfasalazine were found to prevent CXCL8 production by SPLA₂-IB in human neutrophils. In addition, the signaling events induced by SPLA₂-IB included activation of the MAPK ERK and an increase in intracellular Ca²⁺, which are both required for CXCL8 production. The exogenous addition of SPLA₂-IB did not induce arachidonic acid release from human neutrophils, and the inactivation of SPLA₂-IB by EGTA did not affect CXCL8 production by SPLA₂-IB in human neutrophils. Taken together, we suggest that SPLA₂-IB plays a role in the modulation of ioiammatory and immune responses via the SPLA₂ receptor, by inducing CXCL8 in human neutrophils.