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 Inflammjournal_title
Mediators of inflammationauthors
Misdaq M,Ziegler S,von Ahsen N,Oellerich M,Asif ARdoi
10.1155/2015/434825subject
Has Abstractpub_date
2015-01-01 00:00:00pages
434825eissn
0962-9351issn
1466-1861journal_volume
2015pub_type
杂志文章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
更新日期:2018-03-11 00:00:00
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
更新日期:2020-04-03 00:00:00
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
更新日期:2016-01-01 00:00:00
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
更新日期:2011-01-01 00:00:00
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
更新日期:2018-12-10 00:00:00
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
更新日期:1993-01-01 00:00:00
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
更新日期:2012-01-01 00:00:00
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
更新日期:2015-01-01 00:00:00
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
更新日期:2017-01-01 00:00:00
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
更新日期:2014-01-01 00:00:00
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
更新日期:2006-01-01 00:00:00
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
更新日期:2017-01-01 00:00:00
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
更新日期:2017-01-01 00:00:00
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
更新日期:2016-01-01 00:00:00
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
更新日期:2007-01-01 00:00:00
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
更新日期:2013-01-01 00:00:00
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
更新日期:2020-10-22 00:00:00
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
更新日期:2002-10-01 00:00:00
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
更新日期:2011-01-01 00:00:00
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
更新日期:2017-01-01 00:00:00
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
更新日期:2015-01-01 00:00:00
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
更新日期:2017-01-01 00:00:00
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
更新日期:2016-01-01 00:00:00
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
更新日期:1996-01-01 00:00:00
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
更新日期:2016-01-01 00:00:00
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
更新日期:2020-09-29 00:00:00
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
更新日期:2015-01-01 00:00:00
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
更新日期:1993-01-01 00:00:00
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
更新日期:1998-01-01 00:00:00
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
更新日期:2015-01-01 00:00:00