Knockdown of PLCε inhibits inflammatory cytokine release via STAT3 phosphorylation in human bladder cancer cells

Phospholipase Ce (PLCe) is a multifunctional enzyme implicated in inflammatory functions. There are limited data, however, on how PLCe can alter inflammatory cytokine by affecting downstream pathways. Recent studies suggest that inflammation is likely to have an important role in transitional cell carcinoma of bladder (TCCB) and cancer disease progression. Here, we showed that PLCe and p-STAT3 expression were both elevated in TCCB tissues compared to adjacent tissues, and the increase of PLCe level was associated with the increase of p-STAT3 level. Then, knockdown of PLCe using adenovirus-shPLCe significantly decreased inflammatory cytokine (IL-6, TNF-α, IL-1β) expression and inflammation-associated gene (TLR4, MyD88, p-STAT3) expression. Furthermore, we demonstrated that PLCe knockdown blocked LPS-induced inflammatory cytokine and p-STAT3 expression. Additionally, we found that combined treatment of STAT3 inhibitor S3I-201 with adenovirus-shPLCe exhibited synergistic inhibitory effects on expression of p-STAT3. Our results suggested that STAT3 phosphorylation is involved in PLCe-mediated inflammatory cytokine release. Our research is of potential importance in drug development programs using PLCe as a therapeutic target for TCCB.