title: Pristane induces autophagy in macrophages, promoting a STAT1-IRF1-TLR3 pathway and arthritis.
abstract: Autophagy is involved in both innate and adaptive immune regulation. We propose that autophagy regulates activation of TLR3 in macrophages and is thereby essential for development of pristane-induced arthritis. We found that pristane treatment induced autophagy in macrophages in vitro and in vivo, in spleen cells from pristane injected rats. The induced autophagy was associated with STAT1 phosphorylation and expression of IRF1 and TLR3. Blocking the pristane activated autophagy by Wortmannin and Bafilomycin A1 or by RNAi of Becn1 led to a downregulation of the associated STAT1-IRF1-TLR3 pathway. Most importantly, the development of arthritis was alleviated by suppressing either autophagy or TLR3. We conclude that pristane enhanced autophagy, leading to a STAT1-IRF1 controlled upregulation of TLR3 expression in macrophages, is a pathogenic mechanism in the development of arthritis.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China; Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: zhuwenhua@xjtu.edu.cn.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: ccathy0921@gmail.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: jiangcongshan@xjtu.edu.cn.
authors.forename: Congshan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: realwbo@gmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: gengmanman@stu.xjtu.edu.cn.
authors.forename: Manman
authors.initials: M
authors.lastname: Geng
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: wxykle@163.com.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: Saithy1223@yahoo.com.
authors.forename: Nazim
authors.initials: N
authors.lastname: Hussain
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: gaoningzq@163.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Gao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: hanyan@xjtu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: lidongm@xjtu.edu.cn.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: lanxi.118@stu.xjtu.edu.cn.
authors.forename: Xi
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: nqlan@xjtu.edu.cn.
authors.forename: Qilan
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: zfj@xjtu.edu.cn.
authors.forename: Fujun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: Rikard.Holmdahl@ki.se.
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China; Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: mengliesu@mail.xjtu.edu.cn.
authors.forename: Liesu
authors.initials: L
authors.lastname: Meng
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: lushemin@mail.xjtu.edu.cn.
authors.forename: Shemin
authors.initials: S
authors.lastname: Lu
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D050856:Interferon Regulatory Factor-1; C494259:Irf1 protein, rat; D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; C530472:TLR3 protein, rat; D013729:Terpenes; D051196:Toll-Like Receptor 3; C009042:pristane
keywords: Autophagy; Experimental arthritis; Gene expression; Macrophages; TLR3