Knockdown of CXCL3-inhibited apoptosis and inflammation in lipopolysaccharide-treated BEAS-2B and HPAEC through inactivating MAPKs pathway.

Abstract

CXCL3 (C-X-C motif chemokine ligand 3) is a member of chemokines family, which binds to the receptor to recruit neutrophils to lungs, thus participating in the pathogenesis of asthmatic lung. The role of CXCL3 in sepsis-induced acute lung injury is investigated here. Human lung epithelial cell line (BEAS-2B) and human pulmonary artery endothelial cell line (HPAEC) were treated with lipopolysaccharides (LPS). MTT and flow cytometry were performed to detect cell viability and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to assess the levels of inflammatory factors. Treatment with LPS resulted in the decrease of cell viability in BEAS-2B and HPAEC. CXCL3 was particularly upregulated in LPS-treated BEAS-2B and HPAE cells. Knockdown of CXCL3 enhanced viability and suppressed apoptosis i006E LPS-treated BEAS-2B and HPAE cells. Knockdown of CXCL3 also upregulated TNF-α, IL-1β, and IL-18 in LPS-treated BEAS-2B and HPAE cells. Moreover, knockdown of CXCL3 suppressed the activation of mitogen-activated protein kinases (MAPKs) signaling in LPS-treated BEAS-2B and HPAE cells through downregulation of p-ERK1/2, p-p38, and p-JNK. On the other hand, overexpression of CXCL3 caused completely opposite results in LPS-treated BEAS-2B and HPAE cells. Knockdown of CXCL3 exerted antiapoptotic and anti-inflammatory effects against LPS-treated BEAS-2B and HPAE cells, at least partially, through inactivation of MAPKs signaling, suggesting a potential strategy for the intervention of sepsis-induced acute lung injury.