title: Resistin stimulates expression of chemokine genes in chondrocytes via combinatorial regulation of C/EBPβ and NF-κB.
abstract: To further investigate the regulation role of two chemokine genes CCL3 and CCL4 in chondrocytes in response to resistin, human primary chondrocytes and T/C-28a2 cells were cultured. The function of resistin on the chemokine genes, and the expression of C/EBPβ, NF-κB isoforms were tested using qPCR. The methods used to investigate timed co-regulation of C/EBPβ and NF-κB were NF-κB inhibitor (IKK-NBD) and C/EBPβ inhibitor (SB303580) treatments, and subcellular localization, with or without resistin stimulation. Results showed that resistin could increase the up-regulation of chemokine genes independently. Resistin increased the expression of C/EBPβ and NF-κB isoforms. C/EBPβ regulated basal activity and steadily increased over time up to 24h with resistin. NF-κB was up-regulated upon induction with resistin, peaking at 4 h. C/EBPβ and NF-κB co-enhanced the chemokines expression; inhibition of their activity was additive. The timing of activation in chondrocytes was confirmed by subcellular localization of C/EBPβ and c-rel. Chondrocytes react to resistin in a non-restricted cell-specific manner, utilizing C/EBPβ and NF-κB in a combinatorial regulation of chemokine gene expression. The activity of C/EBPβ is augmented by a transient increase in activity of NF-κB, and both transcription factors act independently on the chemokine genes, CCL3 and CCL4. Thus, resistin stimulates CCL3 and CCL4 through combinatorial regulation of C/EBPβ and NF-κB in chondrocytes.
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. zhangziji1984@163.com.
authors.forename: Ziji
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. zhzhiqi@163.com.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. neokang@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. changhe713@sina.com.
authors.forename: Changhe
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. xind@wudosis.wustl.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. shengpuyi@hotmail.com.
authors.forename: Puyi
authors.initials: P
authors.lastname: Sheng
authors.affiliation: Department of Orthopaedic Surgery, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO 63110, USA. sandelll@wustl.edu.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Sandell
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. liaowmsysu@163.com.
authors.forename: Weiming
authors.initials: W
authors.lastname: Liao
mesh_terms: D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D054407:Chemokine CCL4 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D052243:Resistin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D016328:NF-kappa B; D020033:Protein Isoforms; D012333:RNA, Messenger; D052243:Resistin