title: PPARγ agonist suppresses TLR4 expression and TNF-α production in LPS stimulated monocyte leukemia cells.
abstract: It has been well established that inflammation plays a critical role in cancer. Chronic inflammation promotes tumorgenesis and metastasis, which suggests that anti-inflammation drugs could act as a tumor suppressor. It is known that the peroxisome proliferator-activated receptor γ (PPARγ) has been implicated in anti-inflammatory responses; however, the anti-tumor effects of PPARγ have not been intensively investigated. In this study, we examined the effects of PPARγ in cancer. We show that the activation of PPARγ by its agonist rosiglitazone (RGZ) reduces cell proliferation rate in inflammatory and tumor-derived U937 cells. Treatment of RGZ suppresses the expression Toll-like receptor 4 (TLR4) and decreases the production of TNF-α in LPS treated U937 cells. This suggests that NF-κB signaling may be involved in anti-tumor effect of RGZ. Our results demonstrate a role of PPARγ in regulation of NF-κB signaling by modulating TLR4 expression and TNF-α production.
authors.affiliation: Hematological Department and Research Institute, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong, People's Republic of China.
authors.forename: Chun-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Fang
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Lin
authors.forename: Ruo-Zhi
authors.initials: RZ
authors.lastname: Xiao
authors.forename: Ren-Wei
authors.initials: RW
authors.lastname: Huang
authors.forename: He-Qing
authors.initials: HQ
authors.lastname: Huang
authors.forename: Pei-Qing
authors.initials: PQ
authors.lastname: Liu
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Liu
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone