title: Emodin suppresses LPS-induced inflammation in RAW264.7 cells through a PPARγ-dependent pathway.
abstract: Inflammation is a defense and protective response to multiple harmful stimuli. Over and uncontrolled inflammation can lead to local tissues or even systemic damages and injuries. Actually, uncontrolled and self-amplified inflammation is the fundament of the pathogenesis of a variety of inflammatory diseases, including sepsis shock, acute lung injury and acute respiratory distress syndrome (ALI/ARDS). Our recent study showed that emodin, the main active component of Radix rhizoma Rhei, could significantly ameliorate LPS-induced ALI/ARDS in mice. However, its underlying signal pathway was not still very clear. Then, the aim of current study was to explore whether emodin could attenuate LPS-induced inflammation in RAW264.7 cells, and its involved potential mechanism. The mRNA and protein expression of ICAM-1, MCP-1 and PPARγ were measured by qRCR and western blotting, the production of TNF-α was evaluated by ELISA. Then, the phosphorylation of NF-κB p65 was also detected by western blotting. And NF-κB p65 DNA binding activity was analyzed by ELISA as well. Meanwhile, siRNA-PPARγ transfection was performed to knockdown PPARγ expression in cells. Our data revealed that LPS-induced the up-regulation of ICAM-1, MCP-1 and TNF-α, LPS-induced the down-regulation of PPARγ, and LPS-enhanced NF-κB p65 activation and DNA binding activity were substantially suppressed by emdoin in RAW264.7 cells. Furthermore, our data also figured out that these effects of emdoin were largely abrogated by siRNA-PPARγ transfection. Taken together, our results indicated that LPS-induced inflammation were potently compromised by emodin very likely through the PPARγ-dependent inactivation of NF-κB in RAW264.7 cells.
authors.affiliation: Respiratory Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Respiratory Medicine, First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Neurology Department, Handan Central Hospital, Hebei, Handan 056001, China.
authors.forename: She-Jun
authors.initials: SJ
authors.lastname: Feng
authors.affiliation: Respiratory Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China. Electronic address: yuhuapeng2013@163.com.
authors.forename: Hua-Peng
authors.initials: HP
authors.lastname: Yu
mesh_terms: D031841:Aconitum / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004642:Emodin / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D034741:RNA, Small Interfering / Q000235:genetics; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D034741:RNA, Small Interfering; D004642:Emodin
keywords: Emodin; Inflammation; Nuclear factor-κB (NF-κB); Peroxisome proliferators-activated receptor γ (PPARγ); RAW264.7 cells