title: Peoniflorin suppresses tumor necrosis factor-α induced chemokine production in human dermal microvascular endothelial cells by blocking nuclear factor-κB and ERK pathway.
abstract: Peoniflorin (PF) extracted from the root of Paeonia lactiflora pall displays anti-inflammation and antioxidant properties in several animal models. Chemokines are vital for directing the movement of circulating leukocytes to the sites of inflammation and are involved in the pathogenesis of various inflammatory skin diseases. Herein, we investigated the effects and potential mechanisms of PF on tumor necrosis factor-α (TNF-α) induced chemokine production in human dermal microvascular endothelial cells. Human dermal microvascular endothelial cell line (HMEC-1) was treated by TNF-α with or without PF. PF markedly attenuated TNF-α-induced chemokines (including CCL2, CCL5, CCL20, CXCL8, CXCL16 and CX3CL1) mRNA expression in HMEC-1. PF also reduced the secretion of these chemokines in culture supernatants. In addition, endothelial activation in the presence of PF markedly blocked the chemotactic activities of TNF-α-stimulated HMEC-1 supernatant on promyelocytic leukemia cell line (HL-60) or the acute mature monocytic leukemia cell line (THP-1) cell migration. Furthermore, Western blot data revealed TNF-α upregulated phosphorylation of inhibitor of κB-α (IκBα) and phosphorylation of extracellular signal-regulated kinase (ERK)1/2, which was almost completely reversed by PF. Finally, PF inhibited nuclear factor-κB (NF-κB) nuclear translocation to the nucleus. Taken together, our data provide the first evidence that PF has an anti-inflammatory ability against TNF-α-induced chemokine production and leukocyte migration, which may be at least partly related to the inhibition of NF-κB and ERK pathway. PF may be a candidate medicine for the treatment of inflammatory skin diseases.
authors.affiliation: Department of Dermatovenereology, West China Hospital of Sichuan University, Guoxue Alley, Chengdu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Zai-Pei
authors.initials: ZP
authors.lastname: Guo
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Jiao
authors.forename: Rui-Zhen
authors.initials: RZ
authors.lastname: Jia
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Li
authors.forename: Xu-Lei
authors.initials: XL
authors.lastname: Huang
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Liu
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D039821:Monoterpenes; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D006027:Glycosides
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001565:Benzoates; D001952:Bridged-Ring Compounds; D018925:Chemokines; D048049:Extracellular Signal-Regulated MAP Kinases; D005960:Glucosides; D051550:I-kappa B Kinase; D039821:Monoterpenes; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C015423:peoniflorin; D006027:Glycosides