title: CD200Fc reduces LPS-induced IL-1β activation in human cervical cancer cells by modulating TLR4-NF-κB and NLRP3 inflammasome pathway.
abstract: Chronic inflammation plays an important role in tumorigenesis of cervical cancer. CD200Fc, a CD200R1 agonist, has been found to have anti-inflammatory effects in autoimmune diseases and neuro-degeneration. However, the anti-inflammatory effect of CD200Fc on cervical cancer has not yet to be completely understood. This study investigated the anti-inflammatory effects and mechanisms of CD200Fc in LPS-induced human SiHa cells and Caski cells. SiHa cells and Caski cells were stimulated with 40 μg/ml LPS under different concentrations of CD200Fc for 90 min or 12 hours. The mRNA and protein levels of pro-IL-1β, cleaved-IL-1β and NLRP3, as well as the protein level of cleaved caspase-1, were significantly increased in LPS-induced SiHa cells and Caski cells. LPS stimulation did not change ASC and pro-caspase-1 expression. CD200Fc down-regulated protein expression of cleaved caspase-1 and mRNA and protein expression of pro-IL-1β, cleaved-IL-1β and NLRP3. In addition, the protein levels of TLR4, p-P65 and p-IκB, as well as the translocation of P65 to nucleus, were significantly increased in LPS-induced SiHa cells and Caski cells. LPS stimulation did not change t-P65 and t-IκB on protein levels, which were components of TLR-NF-κB pathway. CD200Fc down-regulated protein expression of TLR4, p-P65 and p-IκB and inhibited the translocation of P65 to nucleus in LPS-induced SiHa cells and Caski cells. These results indicated that CD200Fc appeared to suppress the inflammatory activity of TLR4-NF-κB and NLRP3 inflammasome pathway in LPS-induced SiHa cells and Caski cells. It provided novel mechanistic insights into the potential therapeutic uses of CD200Fc for cervical cancer.
authors.affiliation: Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China.
authors.forename: Aiqin
authors.initials: A
authors.lastname: He
authors.affiliation: Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Yunzhao
authors.initials: Y
authors.lastname: Xu
mesh_terms: D020170:Caspase 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: C529001:CD200-FC, mouse; D007074:Immunoglobulin G; D058847:Inflammasomes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D051197:Toll-Like Receptor 4; D020170:Caspase 1
keywords: CD200Fc; IL-1β; NLRP3 inflammasome; TLR4-NF-κB; cervical cancer