title: Paeoniflorin suppresses IL-6/Stat3 pathway via upregulation of Socs3 in dendritic cells in response to 1-chloro-2,4-dinitrobenze.
abstract: Mounting evidence has suggested that inflammation is associated with IL-6/Stat3 pathway in dendritic cells (DCs) and Th17 cells, which are critical for development of allergic contact dermatitis (ACD). Paeoniflorin (PF) has been clinically proved to be effective in the treatment of inflammatory skin diseases such as ACD. We have previously demonstrated the effect of PF on DCs stimulated with 1-chloro-2,4-dinitrobenze (DNCB) and naïve CD4(+)CD45RA(+) T cells for Th17 cell differentiation. However, whether PF down-regulates IL-6/Stat3 in DCs and Th17 cells remains to be explored. In this study, we show clearly that PF markedly decreases IL-6/Stat3 in DCs stimulated with DNCB at both gene and protein levels compared with control DCs in vitro. Meanwhile, PF up-regulates suppressor of cytokine signaling 3 (Socs3). Such decreased expression of IL-6/Stat3 is abolished in DCs that were transfected with Socs3 short interfering RNA (siRNA). When mice CD4(+)CD45 RA(+) T cells were co-cultured with PF-treated DCs stimulated with/without DNCB, the gene expression of the Th17 cell markers such as retinoic acid-related orphan nuclear hormone receptor γt (RORγt), IL-17A, and IL-23R decreased, in accordance with the less secretions of IL-17 and IL-23 in vitro and in vivo. Finally, the suppressed Th17 differentiation induced by PF can be abolished by additional recombinant mouse IL-6. Our results suggest that the anti-inflammatory mechanisms introduced by depletion of Socs3 expression or inactivation of the negative regulator such as Socs3 may represent a promising strategy for the prevention of ACD.
authors.affiliation: Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China; Department of Dermatology, Jining No. 1 People's Hospital, Shandong, PR China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Microbiology/Immunology, Georgetown University Medical Center, Washington DC, USA.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China.
authors.forename: Yongnian
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Dermatology, Jining No. 1 People's Hospital, Shandong, PR China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Dermatology, Jining No. 1 People's Hospital, Shandong, PR China.
authors.forename: Tianhang
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Mei
authors.affiliation: Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China.
authors.forename: Guixia
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Dermatology, Jining No. 1 People's Hospital, Shandong, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Dermatology, The Affiliated Hospital of Qingdao University, Qingdao University,Shandong, PR China. Electronic address: chenguanzhiqd@126.com.
authors.forename: Guanzhi
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China. Electronic address: liumyco@hotmail.com.
authors.forename: Weida
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy / Q000276:immunology; D004137:Dinitrochlorobenzene / Q000276:immunology; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D039821:Monoterpenes / Q000494:pharmacology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology*; D006027:Glycosides
chemical_list: D000893:Anti-Inflammatory Agents; D004137:Dinitrochlorobenzene; D005960:Glucosides; D015850:Interleukin-6; D039821:Monoterpenes; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; C015423:peoniflorin; D006027:Glycosides
keywords: Allergic contact dermatitis; Dendritic cells; Paeoniflorin; Suppressor of cytokine signaling (Socs); Th17 cells