PLCB3 cooperates with the Toll-like receptors' signaling cascade enhancing P.aeruginosa-dependent IL-8 expression in bronchial epithelial cells

An excessive neutrophilic inflammation, initially orchestrated by bronchial epithelial cells and amplified by chronic bacterial infection with P.aeruginosa, leads to progressive tissue destruction in the lungs of patients affected by Cystic Fibrosis. The discovery of novel molecular targets may help to develop more effective anti-inflammatory drugs. In this issue, we report that association study conducted on a cohort of F508del homozygous cystic fibrosis patients with either severe or mild progression of lung disease, showed the implication of the nonsynonymous single-nucleotide polymorphism C2534T of the phospholipase C-3 (PLCB3) gene in the neutrophil recruitment. Studies performed in IB3-1 and CuFi-1 bronchial epithelial cells exposed to P.aeruginosa revealed that PLCB3 is implicated in ATP releasing from the cells and subsequent activation of purinergic receptors, intracellular calcium (Ca2+)i signaling, activation of the protein kinase C and C and of the nuclear transcription factor NF-B p65. Thus, the pro-inflammatory pathway regulated by PLCB3 acts by potentiating the Toll-like Receptors’ signaling cascade leading to enhanced IL-8 expression in bronchial epithelial cells. Concluding, PLCB3 may represent an interesting molecular target to attenuate the excessive recruitment of neutrophils without completely abolishing the immune response.