title: A novel inflammatory regulator TIPE2 inhibits TLR4-mediated development of colon cancer via caspase-8.
abstract: OBJECTIVE
  TIPE2 is a novel inflammation regulator, and the role of TIPE2 in colitis-induced colon cancer is not clear. The aim of this study was to test whether TIPE2 inhibits TLR4 pathway in colon cancer patients and to explore potential mechanism of TIPE2 in colon cancer by caspase-8.
  
  
  METHODS
  Expression of TIPE2 and TLR4 in human colon cancer tissues and cell line HT-29 was detected by immunohistochemistry or real-time PCR. TIPE2 mRNA was suppressed by siRNA transfection and the transfection efficiency was proved by fluorescence microscopy and real-time PCR. TLR4 pathway was activated by treating the cells with 1 μg/ml LPS for 4 h. Caspase-8 activities were tested by colorimetric assay in four HT-29 cell groups.
  
  
  RESULTS
  TIPE2 was expressed in the cytoplasm of colon cancer tissues and HT-29 cells. TIPE2 expression was more pronounced in colon cancer tissues compared to normal controls and it was related with lymph node metastasis and Dukes stage of colon cancer. TIPE2 expression was positively correlated with that of TLR4 in colon cancer (r=0.7354). TIPE2 expression was knocked down successfully by siRNA transfection. Caspase-8 activity was elevated both in TIPE2 knockdown cells and in TLR4 activated cells compared to wild-type cells (P< 0.05). And the caspase-8 activity was further increased in TIPE2 knockdown cells after TLR4 was activated (P < 0.05).
  
  
  CONCLUSIONS
  TIPE2 can inhibit caspase-8 activity in colon cancer cells. TIPE2 can regulate TLR4 inflammatory effect and inhibit further amplification of cascade reaction via caspase-8, which provides one new therapeutic target for clinical treatment schedule.
authors.affiliation: Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Li
authors.affiliation: Medical School of Shandong University, Jinan, Shandong, China.
authors.forename: Jing-Ran
authors.initials: JR
authors.lastname: Su
authors.affiliation: Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, Heze Municipal Hospital, Heze, Shandong, China.
authors.forename: Zhao-Ling
authors.initials: ZL
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, Laiwu People's Hospital, Laiwu, Shandong, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D063646:Carcinogenesis; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014162:Transfection
chemical_list: D061945:Caspase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; C552057:TNFAIP8L2 protein, human; D051197:Toll-Like Receptor 4; C505530:CASP8 protein, human; D053181:Caspase 8
keywords: TIPE2; TLR4; caspase-8; colon; inflammation; tumorigenesis