Thiopurines induce oxidative stress in T-lymphocytes: a proteomic approach.

Abstract:

:Thiopurines are extensively used immunosuppressants for the treatment of inflammatory bowel disease (IBD). The polymorphism of thiopurine S-methyltransferase (TPMT) influences thiopurine metabolism and therapy outcome. We used a TPMT knockdown (kd) model of human Jurkat T-lymphocytes cells to study the effects of treatment with 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) on proteome and phosphoproteome. We identified thirteen proteins with altered expression and nine proteins with altered phosphorylation signals. Three proteins (THIO, TXD17, and GSTM3) with putative functions in cellular oxidative stress responses were altered by 6-TG treatment and another protein PRDX3 was differentially phosphorylated in TPMT kd cells. Furthermore, reactive oxygen species (ROS) assay results were consistent with a significant induction of oxidative stress by both TPMT knockdown and thiopurine treatments. Immunoblot analyses showed treatment altered expression of key antioxidant enzymes (i.e., SOD2 and catalase) in both wt and kd groups, while SOD1 was downregulated by 6-TG treatment and TPMT knockdown. Collectively, increased oxidative stress might be a mechanism involved in thiopurine induced cytotoxicity and adverse effects (i.e., hepatotoxicity) and an antioxidant cotherapy might help to combat this. Results highlight the significance of oxidative stress in thiopurines' actions and could have important implications for the treatment of IBD patients.

journal_name

Mediators Inflamm

authors

Misdaq M,Ziegler S,von Ahsen N,Oellerich M,Asif AR

doi

10.1155/2015/434825

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

434825

eissn

0962-9351

issn

1466-1861

journal_volume

2015

pub_type

杂志文章
  • IL-33/IL-31 Axis: A Potential Inflammatory Pathway.

    abstract::Cytokines play an important role in the regulation of the immune system (adaptive and innate). Given their importance in proinflammatory processes, cytokines have been used for understanding the pathogenesis and as biomarkers in many diseases. IL-31 and IL-33 are still considered novel cytokines. IL-31 controls signal...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章,评审

    doi:10.1155/2018/3858032

    authors: Di Salvo E,Ventura-Spagnolo E,Casciaro M,Navarra M,Gangemi S

    更新日期:2018-03-11 00:00:00

  • Dexmedetomidine Protects against Ischemia and Reperfusion-Induced Kidney Injury in Rats.

    abstract::Acute kidney injury (AKI), a clinical syndrome, is a sudden onset of kidney failure that severely affects the kidney tubules. One potential treatment is dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist that is used as an anesthetic adjuvant. It also has anti-inflammatory, neuroprotective, and sympat...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2020/2120971

    authors: Bao N,Dai D

    更新日期:2020-04-03 00:00:00

  • Tumor Necrosis Factor Alpha Inhibits L-Type Ca(2+) Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway.

    abstract::Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca(2+) channel (L-VDCC) current in cardiac myocytes, an observation that seems parado...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2016/5972302

    authors: Reyes-García J,Flores-Soto E,Solís-Chagoyán H,Sommer B,Díaz-Hernández V,García-Hernández LM,Montaño LM

    更新日期:2016-01-01 00:00:00

  • Gene expression profiling in lungs of chronic asthmatic mice treated with galectin-3: downregulation of inflammatory and regulatory genes.

    abstract:BACKGROUND:Asthma is a disorder characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins act as negative regulators of cytokine signaling. In particular, SOCS1 and SOCS3 play an important role in immune response by controlling the balance between Th1 ...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2011/823279

    authors: López E,Zafra MP,Sastre B,Gámez C,Lahoz C,del Pozo V

    更新日期:2011-01-01 00:00:00

  • Metabolism Plays a Key Role during Macrophage Activation.

    abstract::Monocyte and macrophage diversity is evidenced by the modulation of cell surface markers and differential production of soluble mediators. These immune cells play key roles in controlling tissue homeostasis, infections, and excessive inflammation. Macrophages remove dead cells in a process named efferocytosis, contrib...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章,评审

    doi:10.1155/2018/2426138

    authors: Stunault MI,Bories G,Guinamard RR,Ivanov S

    更新日期:2018-12-10 00:00:00

  • Pulmonary granulocyte influx and impaired alveolar macrophage adenylyl cyclase responsiveness in developing respiratory distress.

    abstract::Alveolar macrophages have recently been postulated as being involved in the aetiology of adult respiratory distress syndrome (ARDS). To evaluate their role, basal cyclic AMP levels and responsiveness of adenylyl cyclase alveolar macrophages were determined at four intermediate stages of developing respiratory distress...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/S0962935193000341

    authors: Amsterdam JG,Heijde RM,Grotjohan HP,Beusenberg FD

    更新日期:1993-01-01 00:00:00

  • Effect of magnolol on the function of osteoblastic MC3T3-E1 cells.

    abstract:OBJECTIVES:In the present study, the ability of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, to stimulate osteoblast function and inhibit the release of bone-resorbing mediators was investigated in osteoblastic MC3T3-E1 cells. METHODS:Osteoblast function was measured by cell growth, a...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2012/829650

    authors: Kwak EJ,Lee YS,Choi EM

    更新日期:2012-01-01 00:00:00

  • Neutrophilic Bronchial Inflammation Correlates with Clinical and Functional Findings in Patients with Noncystic Fibrosis Bronchiectasis.

    abstract::Background. Neutrophilic bronchial inflammation is a main feature of bronchiectasis, but not much is known about its relationship with other disease features. Aim. To compare airway inflammatory markers with clinical and functional findings in subjects with stable noncystic fibrosis bronchiectasis (NCFB). Methods. 152...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2015/642503

    authors: Dente FL,Bilotta M,Bartoli ML,Bacci E,Cianchetti S,Latorre M,Malagrinò L,Nieri D,Roggi MA,Vagaggini B,Paggiaro P

    更新日期:2015-01-01 00:00:00

  • Short-Term Regulation of FcγR-Mediated Phagocytosis by TLRs in Macrophages: Participation of 5-Lipoxygenase Products.

    abstract::TLRs recognize a broad spectrum of microorganism molecules, triggering a variety of cellular responses. Among them, phagocytosis is a critical process for host defense. Leukotrienes (LTs), lipid mediators produced from 5-lipoxygenase (5-LO) enzyme, increase FcγR-mediated phagocytosis. Here, we evaluated the participat...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2017/2086840

    authors: Pinheiro CDS,Monteiro APT,Dutra FF,Bozza MT,Peters-Golden M,Benjamim CF,Canetti C

    更新日期:2017-01-01 00:00:00

  • Macrophage P2X7 receptor function is reduced during schistosomiasis: putative role of TGF- β1.

    abstract::Schistosomiasis is a chronic inflammatory disease whose macrophages are involved in immunopathology modulation. Although P2X7 receptor signaling plays an important role in inflammatory responses mediated by macrophages, no reports have examined the role of P2X7 receptors in macrophage function during schistosomiasis. ...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2014/134974

    authors: Oliveira SD,Nanini HF,Savio LE,Waghabi MC,Silva CL,Coutinho-Silva R

    更新日期:2014-01-01 00:00:00

  • Flunisolide decreases exhaled nitric oxide and nitrotyrosine levels in asthmatic children.

    abstract:BACKGROUND:Exhaled nitric oxide (FeNO) has been reported to be elevated in the oxidative stress involved in asthmatic patients, and the reaction of nitric oxide (NO) with superoxide anions results in the formation of nitrotyrosine. The purpose of this study was to investigate the effect of inhaled steroid treatment on ...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/MI/2006/31919

    authors: Bodini A,Peroni DG,Zardini F,Corradi M,Alinovi R,Boner AL,Piacentini GL

    更新日期:2006-01-01 00:00:00

  • The Role of Proinflammatory Pathways in the Pathogenesis of Colitis-Associated Colorectal Cancer.

    abstract::Patients with inflammatory bowel disease (IBD) are at an increased risk of developing colorectal cancer (CRC). The risk factors of CRC in IBD patients include long disease duration, extensive colitis, severe histological inflammation, and coexistence with primary sclerosing cholangitis (PSC). Several molecular pathway...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章,评审

    doi:10.1155/2017/5126048

    authors: Luo C,Zhang H

    更新日期:2017-01-01 00:00:00

  • Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4+CD25+ Regulatory T Cells Mainly through Axl Receptor.

    abstract::Background. Growth arrest-specific (Gas) 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk), and its role as an immune modulator has been recently emphasized. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the active suppression of autoimmunity. The present study wa...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2017/6848430

    authors: Zhao GJ,Zheng JY,Bian JL,Chen LW,Dong N,Yu Y,Hong GL,Chandoo A,Yao YM,Lu ZQ

    更新日期:2017-01-01 00:00:00

  • Recent Advances in Antiviral Therapy for Chronic Hepatitis C.

    abstract::Hepatitis C virus (HCV) infection is a major worldwide health problem. Chronic infection induces continuous inflammation in the liver, progression of hepatic fibrosis, eventual cirrhosis, and possible hepatocellular carcinoma. Eradication of the virus is one of the most important treatment aims. A number of promising ...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章,评审

    doi:10.1155/2016/6841628

    authors: Tamori A,Enomoto M,Kawada N

    更新日期:2016-01-01 00:00:00

  • The level of hs-CRP in coronary artery ectasia and its response to statin and angiotensin-converting enzyme inhibitor treatment.

    abstract:BACKGROUND/AIM:Coronary artery ectasia (CAE) was thought of as a variant of atherosclerosis. C-reactive protein (CRP) which is among the most sensitive markers of systemic inflammation, and elevation of systemic and local levels of this inflammatory marker which has been associated with an increased risk for cardiovasc...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2007/89649

    authors: Ozbay Y,Akbulut M,Balin M,Kayancicek H,Baydas A,Korkmaz H

    更新日期:2007-01-01 00:00:00

  • Anti-inflammatory effects of ellagic acid on acute lung injury induced by acid in mice.

    abstract::Acute lung injury (ALI) is characterized by alveolar edema and uncontrolled neutrophil migration to the lung, and no specific therapy is still available. Ellagic acid, a compound present in several fruits and medicinal plants, has shown anti-inflammatory activity in several experimental disease models. We used the non...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2013/164202

    authors: Cornélio Favarin D,Martins Teixeira M,Lemos de Andrade E,de Freitas Alves C,Lazo Chica JE,Artério Sorgi C,Faccioli LH,Paula Rogerio A

    更新日期:2013-01-01 00:00:00

  • Serum and Cerebrospinal Fluid Cytokine Biomarkers for Diagnosis of Multiple Sclerosis.

    abstract:Background:Multiple sclerosis (MS) is a chronic debilitating disorder characterized by persisting damage to the brain caused by autoreactive leukocytes. Leukocyte activation is regulated by cytokines, which are readily detected in MS serum and cerebrospinal fluid (CSF). Objective:Serum and CSF levels of forty-five cyt...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2020/2727042

    authors: Martynova E,Goyal M,Johri S,Kumar V,Khaibullin T,Rizvanov AA,Verma S,Khaiboullina SF,Baranwal M

    更新日期:2020-10-22 00:00:00

  • Annexin 1 localisation in tissue eosinophils as detected by electron microscopy.

    abstract:BACKGROUND:Human and rodent leukocytes express high levels of the glucocorticoid-inducible protein annexin 1 (ANXA1) (previously referred to as lipocortin 1). Neutrophils and monocytes have abundant ANXA1 levels. AIM:We have investigated, for the first time, ANXA1 ultrastructural expression in rat eosinophils and comp...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1080/09629350210000015683

    authors: Oliani SM,Damazo AS,Perretti M

    更新日期:2002-10-01 00:00:00

  • Inflammatory mediators release in urine from mice injected with Crotalus durissus terrificus venom.

    abstract::In this study, we investigated in groups of female BALB/c mice injected with Crotalus durissus terrificus venom (Cdt) the renal function based on creatinine clearance, percentage of fractional excretion cytokines and histological examination of renal tissue. Cdt caused renal alterations that induced proteinuria during...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2011/103193

    authors: Hernández Cruz A,Barbosa Navarro L,Mendonça RZ,Petricevich VL

    更新日期:2011-01-01 00:00:00

  • Intrinsic Properties of Brown and White Adipocytes Have Differential Effects on Macrophage Inflammatory Responses.

    abstract::Obesity is marked by chronic, low-grade inflammation. Here, we examined whether intrinsic differences between white and brown adipocytes influence the inflammatory status of macrophages. White and brown adipocytes were characterized by transcriptional regulation of UCP-1, PGC1α, PGC1β, and CIDEA and their level of IL-...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2017/9067049

    authors: Dowal L,Parameswaran P,Phat S,Akella S,Majumdar ID,Ranjan J,Shah C,Mogre S,Guntur K,Thapa K,Gesta S,Vishnudas VK,Narain NR,Sarangarajan R

    更新日期:2017-01-01 00:00:00

  • Myeloid-Derived Suppressor Cells and Therapeutic Strategies in Cancer.

    abstract::Development of solid cancer depends on escape from host immunosurveillance. Various types of immune cells contribute to tumor-induced immune suppression, including tumor associated macrophages, regulatory T cells, type 2 NKT cells, and myeloid-derived suppressor cells (MDSCs). Growing body of evidences shows that MDSC...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章,评审

    doi:10.1155/2015/159269

    authors: Katoh H,Watanabe M

    更新日期:2015-01-01 00:00:00

  • The Correlation between FSTL1 Expression and Airway Remodeling in Asthmatics.

    abstract:BACKGROUND:Asthma is characterized by airway remodeling. Follistatin-like protein 1 (FSTL1) is an extracellular glycoprotein. Recent studies suggest that FSTL1 may participate in the pathogenesis of asthma. OBJECTIVES:To analyze the association between FSTL1 and some parameters and inspect the role of FSTL1 in asthma....

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2017/7918472

    authors: Liu Y,Liu T,Wu J,Li T,Jiao X,Zhang H,Zhao J,Wang J,Liu L,Cao L,Li S,Xu J,Xu J,Ma X,Yang L,Dong L

    更新日期:2017-01-01 00:00:00

  • Role of Mitochondria-Associated Endoplasmic Reticulum Membrane in Inflammation-Mediated Metabolic Diseases.

    abstract::Inflammation is considered to be one of the most critical factors involved in the development of complex metabolic diseases such as type 2 diabetes, cancer, and cardiovascular disease. A few decades ago, the discovery of mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) was followed by the identificati...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章,评审

    doi:10.1155/2016/1851420

    authors: Thoudam T,Jeon JH,Ha CM,Lee IK

    更新日期:2016-01-01 00:00:00

  • The evolution of inflammatory mediators.

    abstract::Invertebrates do not display the level of sophistication in immune reactivity characteristic of mammals and other 'higher' vertebrates. Their great number and diversity of forms, however, reflect their evolutionary success and hence they must have effective mechanisms of defence to deal with parasites and pathogens an...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/S0962935196000014

    authors: Rowley AF

    更新日期:1996-01-01 00:00:00

  • CRP and SAA1 Haplotypes Are Associated with Both C-Reactive Protein and Serum Amyloid A Levels: Role of Suppression Effects.

    abstract::To test the statistical association of the CRP and SAA1 locus variants with their corresponding circulating levels and metabolic and inflammatory biomarker levels by using mediation analysis, a sample population of 599 Taiwanese subjects was enrolled and five CRP and four SAA1 variants were genotyped. Correlation anal...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2016/5830361

    authors: Ko YL,Hsu LA,Wu S,Teng MS,Chou HH

    更新日期:2016-01-01 00:00:00

  • Retracted: The Anti-Inflammatory Effects of Shinbaro3 Is Mediated by Downregulation of the TLR4 Signalling Pathway in LPS-Stimulated RAW 264.7 Macrophages.

    abstract::[This retracts the article DOI: 10.1155/2018/4514329.]. ...

    journal_title:Mediators of inflammation

    pub_type: 撤回出版物

    doi:10.1155/2020/7859157

    authors: Of Inflammation M

    更新日期:2020-09-29 00:00:00

  • Constitutive Activation of the Nlrc4 Inflammasome Prevents Hepatic Fibrosis and Promotes Hepatic Regeneration after Partial Hepatectomy.

    abstract::TThe molecular mechanisms responsible for the development of hepatic fibrosis are not fully understood. The Nlrc4 inflammasome detects cytosolic presence of bacterial components, activating inflammatory cytokines to facilitate clearance of pathogens and infected cells. We hypothesized that low-grade constitutive activ...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/2015/909827

    authors: DeSantis DA,Ko CW,Wang L,Lee P,Croniger CM

    更新日期:2015-01-01 00:00:00

  • LPS-induced serum TNF production and lethality in mice: effect of L-carnitine and some acyl-derivatives.

    abstract::The effect of L-carnitine and some of its acyl derivatives on serum TNF production and lethality in a murine experimental endotoxin shock model was investigated. In some instances, serum IL-6 production was also evaluated. In this experimental model, C57BL/6 mice received 30 mg/kg LPS (E. cell 055:B5) injected intrape...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1155/S0962935193000754

    authors: Ruggiero V,D'Urso CM,Albertoni C,Campo S,Foresta P,Martelli EA

    更新日期:1993-01-01 00:00:00

  • Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis.

    abstract::We investigated the serum concentrations of interleukin-6 (IL-6) and two IL-6 family of cytokines (leukaemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) as well as IL-6 soluble receptor (sIL-6R) using an enzyme-linked immunosorbent assay (ELISA) in 66 patients with rheumatoid arthritis (RA) and 24 h...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章

    doi:10.1080/09629359890875

    authors: Robak T,Gladalska A,Stepień H,Robak E

    更新日期:1998-01-01 00:00:00

  • Mucocutaneous Involvement in Behçet's Disease: How Systemic Treatment Has Changed in the Last Decades and Future Perspectives.

    abstract::Behçet's disease (BD) is a multisystemic disorder of unknown etiology characterized by the "triple symptom complex" consisting of recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis. Recurrent mucocutaneous lesions are generally considered the hallmark of the disease, being the most commo...

    journal_title:Mediators of inflammation

    pub_type: 杂志文章,评审

    doi:10.1155/2015/451675

    authors: Rotondo C,Lopalco G,Iannone F,Vitale A,Talarico R,Galeazzi M,Lapadula G,Cantarini L

    更新日期:2015-01-01 00:00:00