title: Ox-LDL influences peripheral Th17/Treg balance by modulating Treg apoptosis and Th17 proliferation in atherosclerotic cerebral infarction.
abstract: BACKGROUND
  CD4(+)CD25(+) regulatory T (Treg) cells and T-helper 17 (Th17) cells play important roles in acute cerebral infarction (ACI). Our previous findings have suggested that oxidized low-density lipoprotein (Ox-LDL) could influence Treg/Th17 ratio in ACI patients. However, the mechanisms are still not clear.
  
  
  RESULTS
  We evaluated the effects of ox-LDL on Th17/Treg cell apoptosis and proliferation in vitro. Our results demonstrated that with increased ox-LDL concentrations, the frequency and suppressive function of Treg cells was decreased while the frequency of Th17 cells was elevated in control subjects. In addition, AnnexinV(+) apoptotic rate, Fas/Fas ligand (FasL) expression, and Caspase-3 activity were escalated in Treg cells while were no significant changes in Th17 cells. Simultaneously, 5-Bromo-29-Deoxyuridine (BrdU) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyl Tetrazolium Bromide (MTT) incorporation of Th17 cells was elevated accompanied by upregulated nuclear factor-κB (NF-κB) activity. However, Th17 proliferation was decreased when pre-incubated with Pyrrolidine dithiocarbamate (PDTC, inhibitor of NF-κB activation). Furthermore, there were significant changes induced by ox-LDL in Treg apoptosis, Fas/FasL/Caspase-3 expression of Treg cells, and Th17 proliferation, NF-κB activation of Th17 in ACI patients than in patients with transient ischemic attack (TIA) and control subjects (P<0.01, P<0.05 respectively).
  
  
  CONCLUSIONS
  These data support that ox-LDL may influence the Th17/Treg balance by modulating Fasmediated Treg apoptosis and NF-κB-associated Th17 proliferation. Ox-LDL also induced a more significant alteration of Treg and Th17 in ACI patients than in TIA and control groups, suggesting a novel role in the pathogenesis of ACI.
authors: The Central Laboratory of Medical Research Center, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.
authors: Qing
authors: Q
authors: Li
authors: Yiping
authors: Y
authors: Wang
authors: Hongqi
authors: H
authors: Li
authors: Guodong
authors: G
authors: Shen
authors: Shilian
authors: S
authors: Hu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D050197:Atherosclerosis / Q000150:complications; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000097:blood / Q000150:complications / Q000473:pathology; D003430:Cross-Sectional Studies; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood / Q000473:pathology; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D008055:Lipids; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D019014:fas Receptor; C099252:oxidized low density lipoprotein; D053148:Caspase 3