title: CARD15 gene overexpression reduces effect of etanercept, infliximab, and adalimumab on cytokine secretion from PMA activated U937 cells.
abstract: Crohn's disease (CD), a subcategory of inflammatory bowel disease, is an immune-related disorder characterized by inflammation of the gastrointestinal mucosa, which can take place in any region along the alimentary tract. The most important gene involved in the etiology of CD is NOD2/CARD15 located on chromosome 16. It has been shown that CARD15 is overexpressed in monocytes of CD patients. The common treatment for the disease is anti-TNF-alpha drugs, the most hopeful of which are probably infliximab and etanercept. Infliximab rapidly reduces signs and symptoms of active Crohn's disease. In contrast, etanercept shows no such effect. In the present study, we evaluated the effects of the CARD15 gene overexpression in monocytic cell line U937 in the production of anti-inflammatory cytokine, IL-10, and proinflammatory cytokine, Il-1 beta, produced after incubation with infliximab, adalimumab, and etanercept separately. Our results show that infliximab and adalimumab significantly decreased IL-10 and IL-1beta secretion levels. However, etanercept inhibition of secretion was less compared with infliximab or adalimumab. In all three cases, suppression of cytokine production is reduced by CARD15 overexpression.
authors.affiliation: Department of Medical Genetics, Iran University of Medical Sciences, Tehran, Iran; Pediatric Infectious Diseases Research Center, Department of Infectious Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cell and Molecular Biology Department, Pharmaceutical Science Branch, Islamic Azad University, Tehran, Iran. Electronic address: teimourian.sh@iums.ac.ir.
authors.forename: Shahram
authors.initials: S
authors.lastname: Teimourian
authors.affiliation: Pediatric Infectious Diseases Research Center, Department of Infectious Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cell and Molecular Biology Department, Pharmaceutical Science Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Nooshin
authors.initials: N
authors.lastname: Masoudzadeh
mesh_terms: D000068879:Adalimumab / Q000276:immunology / Q000494:pharmacology*; D000068800:Etanercept / Q000276:immunology / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D000069285:Infliximab / Q000276:immunology / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D020298:U937 Cells
chemical_list: D053583:Interleukin-1beta; D053473:Nod2 Signaling Adaptor Protein; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000069285:Infliximab; D000068879:Adalimumab; D013755:Tetradecanoylphorbol Acetate; D000068800:Etanercept
keywords: Adalimumab; CARD15 gene overexpression; Crohn's disease; Etanercept; Infliximab