title: Anti-tumor Necrosis Factor Alpha (Infliximab) Attenuates Apoptosis, Oxidative Stress, and Calcium Ion Entry Through Modulation of Cation Channels in Neutrophils of Patients with Ankylosing Spondylitis.
abstract: Ankylosing Spondylitis (AS) is known to be associated with increased neutrophil activation and oxidative stress, however, the mechanism of neutrophil activation is still unclear. We have hypothesized that the antioxidant and anti-tumor necrosis factor properties of infliximab may affect intracellular Ca(2+) concentration in the neutrophils of AS patients. The objective of this study was to investigate the effects of infliximab on calcium signaling, oxidative stress, and apoptosis in neutrophils of AS patients. Neutrophils collected from ten patients with AS and ten healthy controls were used in the study. In a cell viability test, the ideal non-toxic dose and incubation time of infliximab were found as 100 μM and 1 h, respectively. In some experiments, the neutrophils were incubated with the voltage-gated calcium channel (VGCC) blockers verapamil + diltiazem (V + D) and the TRPM2 channel blocker 2-aminoethyl diphenylborinate (2-APB). Intracellular Ca(2+) concentration, lipid peroxidation, apoptosis, caspase 3, and caspase 9 values were high in neutrophils of AS patients and were reduced with infliximab treatment. Reduced glutathione level and glutathione peroxidase activity were low in the patients and increased with infliximab treatment. The intracellular Ca(2+) concentrations were low in 2-APB and V + D groups. In conclusion, the current study suggests that infliximab is useful against apoptotic cell death and oxidative stress in neutrophils of patients with AS, which seem to be dependent on increased levels of intracellular Ca(2+) through activation of TRPM2 and VGCC.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.
authors.forename: Yunus
authors.initials: Y
authors.lastname: Ugan
authors.affiliation: Neuroscience Research Center, Suleyman Demirel University, 32260, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr.|Department of Microbiology, Faculty of Medicine, Gaziosmanpaşa University, Tokat, Turkey. mustafanaziroglu@sdu.edu.tr.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Nazıroğlu
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Şahin
authors.affiliation: Department of Microbiology, Faculty of Medicine, Gaziosmanpaşa University, Tokat, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Aykur
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D013167:Spondylitis, Ankylosing / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D015220:Calcium Channels; D000069285:Infliximab; D005979:Glutathione Peroxidase; D053148:Caspase 3; D053453:Caspase 9; D005978:Glutathione; D002118:Calcium
keywords: Ankylosing spondylitis; Apoptosis; Calcium signaling; Infliximab; Neutrophil; Oxidative stress