Group IB Secretory Phospholipase A2 Stimulates CXC Chemokine Ligand 8 Production via ERK and NF-κB in Human Neutrophils

Abstract

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 proinflammatory 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 inflammatory and immune responses via the sPLA2 receptor, by inducing CXCL8 in human neutrophils.

Human Serum Mannose-binding Lectin Senses Wall Teichoic Acid Glycopolymer of Staphylococcus aureus, Which Is Restricted in Infancy

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A pertussis toxin sensitive G-protein-independent pathway is involved in serum amyloid A-induced formyl peptide receptor 2-mediated CCL2 production

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LL-37 inhibits serum amyloid A-induced IL-8 production in human neutrophils

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“…The primers used for the RT-PCR analysis have been reported previously (Ushigoe et al, 2000;Jo et al, 2004). The sequences of the primer used were as follows; human IL-8: sense, 5'-ATGACTTCCAAGCTGGCCG-3'; anti-sense, 5'-CTCAGCCCTCTTCAAAAACTT-3'.…”

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