title: Knockdown of PLCε inhibits inflammatory cytokine release via STAT3 phosphorylation in human bladder cancer cells.
abstract: Phospholipase Cε (PLCε) is a multifunctional enzyme implicated in inflammatory functions. There are limited data, however, on how PLCε 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 PLCε and p-STAT3 expression were both elevated in TCCB tissues compared to adjacent tissues, and the increase of PLCε level was associated with the increase of p-STAT3 level. Then, knockdown of PLCε using adenovirus-shPLCε significantly decreased inflammatory cytokine (IL-6, TNF-α, IL-1β) expression and inflammation-associated gene (TLR4, MyD88, p-STAT3) expression. Furthermore, we demonstrated that PLCε knockdown blocked LPS-induced inflammatory cytokine and p-STAT3 expression. Additionally, we found that combined treatment of STAT3 inhibitor S3I-201 with adenovirus-shPLCε exhibited synergistic inhibitory effects on expression of p-STAT3. Our results suggested that STAT3 phosphorylation is involved in PLCε-mediated inflammatory cytokine release. Our research is of potential importance in drug development programs using PLCε as a therapeutic target for TCCB.
authors.affiliation: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, No. 1 Yixueyuan Road, Yu Zhong District, Chongqing, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, No. 1 Yixueyuan Road, Yu Zhong District, Chongqing, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Ou
authors.affiliation: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, No. 1 Yixueyuan Road, Yu Zhong District, Chongqing, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.affiliation: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, No. 1 Yixueyuan Road, Yu Zhong District, Chongqing, People's Republic of China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, No. 1 Yixueyuan Road, Yu Zhong District, Chongqing, People's Republic of China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, No. 1 Yixueyuan Road, Yu Zhong District, Chongqing, People's Republic of China.
authors.forename: E
authors.initials: E
authors.lastname: Chen
authors.affiliation: Department of Urinary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Diao
authors.affiliation: Department of Urinary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Xiaohou
authors.initials: X
authors.lastname: Wu
authors.affiliation: The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, No. 1 Yixueyuan Road, Yu Zhong District, Chongqing, People's Republic of China. luochunli79@126.com.
authors.forename: Chunli
authors.initials: C
authors.lastname: Luo
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D054801:Phosphoinositide Phospholipase C / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D010766:Phosphorylation / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon
keywords: IL-1β; IL-6; PLCε; STAT3; TCCB; TNF-α