title: IL-17A induces pro-inflammatory cytokines production in macrophages via MAPKinases, NF-κB and AP-1.
abstract: BACKGROUND
  Interleukin (IL)-17A, a newly identified cytokine, may participate in the transition of a stable plaque into an unstable plaque. Macrophages play a critical role in the destabilization of atherosclerotic plaque.
  
  
  METHODS
  RAW 264.7 cells were stimulated with IL-17A. The mRNA expression of inflammatory cytokines was determined by RT-PCR. The cytokines production in the supernatants was measured by ELISA. Small interfering RNA (siRNA) was used to confirm that IL-17A-induced pro-inflammatory cytokines production via IL-17RA signaling. The western blot assay was used to detect the phosphorylation of MAPKinases including p38 and ERK1/2. The DNA binding activity of nuclear factor NF-κB and AP-1 were detected by EMSA.
  
  
  RESULTS
  IL-17A induced the production of pro-inflammatory cytokines in macrophages in a time- and dose-dependent manner, such as tumor necrosis factor (TNF)-α, IL-1β, and IL-6. Meanwhile, IL-17A resulted in the phosphorylation of p38 and ERK1/2 and increased DNA-binding activity of NF-κB and AP-1. Pharmacological inhibitors of p38 and ERK1/2 partly attenuated IL-17A-induced TNF-α, IL-1β, and IL-6 production. Either NF-κB inhibitor or AP-1 inhibitor also partly decreased the IL-17A-induced cytokine production.
  
  
  CONCLUSIONS
  IL-17A induces pro-inflammatory cytokines production in macrophages via MAPKinases, NF-κB and AP-1 pathway.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Meng-yang
authors.initials: MY
authors.lastname: Liao
authors.forename: Xing-li
authors.initials: XL
authors.lastname: Gao
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhong
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Tang
authors.forename: Xian
authors.initials: X
authors.lastname: Yu
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Liao
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D053722:Receptors, Interleukin-17; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases