scholarly journals Streptokinase Promotes Development of Dipeptidyl Peptidase IV (CD26) Autoantibodies after Fibrinolytic Therapy in Myocardial Infarction Patients

2002 ◽  
Vol 9 (6) ◽  
pp. 1253-1259 ◽  
Author(s):  
Miguel Cuchacovich ◽  
Héctor Gatica ◽  
Paula Vial ◽  
Jorge Yovanovich ◽  
Salvatore V. Pizzo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Lupus Erythematosus ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Serum Levels ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Necrosis Factor Alpha ◽  
Dpp Iv ◽  
Tnf Α

ABSTRACT Dipeptidyl peptidase IV (DPP IV) (CD26) plays a critical role in the modulation and expression of autoimmune and inflammatory diseases. We recently reported that sera from patients with rheumatoid arthritis and systemic lupus erythematosus contained low levels of DPP IV and high titers of anti-DPP IV autoantibodies of the immunoglobulin A (IgA) and IgG classes and found a correlation between the low circulating levels of DPP IV and the high titers of anti-DPP IV autoantibodies of the IgA class. Since streptokinase (SK) is a potent immunogen and binds to DPP IV, we speculated that patients with autoimmune diseases showed higher DPP IV autoantibody levels than healthy controls as a consequence of an abnormal immune stimulation triggered by SK released during streptococcal infections. We assessed this hypothesis in a group of patients suffering from acute myocardial infarction, without a chronic autoimmune disease, who received SK as part of therapeutic thrombolysis. Concomitant with the appearance of anti-SK antibodies, these patients developed anti-DPP IV autoantibodies. These autoantibodies bind to DPP IV in the region which is also recognized by SK, suggesting that an SK-induced immune response is responsible for the appearance of DPP IV autoantibodies. Furthermore, we determined a correlation between high titers of DPP IV autoantibodies and an augmented clearance of the enzyme from the circulation. Serum levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) increased significantly after 30 days of SK administration, while the levels of soluble IL-2 receptor remained unchanged during the same period, suggesting a correlation between the lower levels of circulating DPP IV and higher levels of TNF-α and IL-6 in serum in these patients.

Critical Role of Dipeptidyl Peptidase IV: A Therapeutic Target for Diabetes and Cancer

2018 ◽  
Vol 19 (2) ◽  
pp. 88-97 ◽  
Author(s):  
Sourav De ◽  
Subhasis Banerjee ◽  
S.K. Ashok Kumar ◽  
Priyankar Paira
Keyword(s):  
Drug Targets ◽  
Critical Role ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Dpp Iv ◽  
Protease Enzyme ◽  
Target Disease ◽  
Dimeric Form ◽  
Epithelium Cells

Diabetes mellitus is an emerging predator and affecting around 422 million adults worldwide. Higher levels of circulating insulin and increased pressure on the pancreas to produce insulin have been inferred as possible etiology for diabetes leading to a higher risk of pancreatic cancer. Out of several drug targets in hypoglycemic discovery, Dipeptidyl peptidase-IV (DPP-IV) has been considered an emerging target. It is a protease enzyme which inactivates incretin hormones i.e., Glucagonlike peptide 1 (GLP-1) and glucose-dependent insulin tropic polypeptide (GIP). Inhibition of DPP-4 results in the longer action of GLP-1 and GIP, therefore, DPP-4 inhibitors play an important role in maintaining glucose homeostasis. In comparison to early oral hypoglycemic, DPP-IV inhibitors are well tolerated and provide a better glycemic control over a longer period. These enzymes are expressed in a dimeric form on the surface of different cells such as prostate, liver and small intestinal epithelium cells. Disruption of the local signaling environment is an emerging factor in cancer development. Till date, not even a single DPP-IV inhibitor as anticancer has been developed. This review focuses on various features of the enzyme and their suitable inhibitors for target disease.

scholarly journals Oxidized cholesterol exacerbates toll-like receptor 4 expression and activity in the hearts of rats with myocardial infarction

2020 ◽  
Vol 12 (1) ◽  
pp. 43-50
Author(s):  
Arash Khorrami ◽  
Mojtaba Ziaee ◽  
Maryam Rameshrad ◽  
Ailar Nakhlband ◽  
Nasrin Maleki-Dizaji ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Oxidized Ldl ◽  
Critical Role ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Normal Diet ◽  
Necrosis Factor Alpha ◽  
Oxidized Cholesterol ◽  
Tlr4 Mrna ◽  
Tnf Α

Introduction: The present study examined the effects of high cholesterol and high oxidized-cholesterol diets on the myocardial expression of TLR4 and pro-inflammatory cytokine in rats.<br /> Methods: Male Wistar rats were allocated into 6 groups and fed with a normal diet, cholesterol, and oxidized-cholesterol rich diets with or without isoproterenol-induced myocardial infarction. TLR4 and MyD 88 expression and levels tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured in the heart and serum. <br /> Results: Oxidized cholesterol-fed animals had higher serum levels of oxidized low-density lipoprotein (LDL) (263 ± 13 ng/dL) than the cholesterol-fed animals (98 ± 8 ng/dL; P < 0.001). A high level of oxidized-LDL caused fibrotic cell formation and enhanced neutrophil infiltration in the absence of MI. Both cholesterol and oxidized-cholesterol upregulated TLR4 mRNA expression and increased TNF-α and IL-6 production in the hearts of rats with MI. In rats fed with oxidized-cholesterol the serum and myocardial levels of TNF-α (653 ± 42 pg/mL, 1375 ± 121 pg/100 mg, respectively) were higher than MI group (358±24 pg/mL, P < 0.001 and 885 ± 56 pg/100 mg, P < 0.01). A significant correlation was seen between TLR4 expression and infarct size.<br /> Conclusion: These findings suggest that cardiac TLR4 is preferentially upregulated by oxidized cholesterol in rats. Oxidized cholesterol may have a critical role in cardiac toxicity in the absence of pathological conditions.

Adenosine deaminase, dipeptidyl peptidase-IV activities and lipid peroxidation are increased in the saliva of obese young adult

2015 ◽  
Vol 53 (7) ◽  
Author(s):  
Eduardo Ottobelli Chielle ◽  
Gabriela Bonfanti ◽  
Karine Santos De Bona ◽  
Rafael Noal Moresco ◽  
Maria Beatriz Moretto
Keyword(s):  
Lipid Peroxidation ◽  
Adenosine Deaminase ◽  
Inflammatory Diseases ◽  
Dipeptidyl Peptidase ◽  
Normal Weight ◽  
Dipeptidyl Peptidase Iv ◽  
Salivary Biomarkers ◽  
The Metabolic Syndrome ◽  
Dpp Iv ◽  
Young Subjects

AbstractObesity is the hallmark of the metabolic syndrome representing a major global health problem. It is considered a state of chronic inflammation with minimal exploration of salivary biomarkers. Thus, the intent of the present study was to assess the activities of salivary dipeptidyl peptidase IV (DPP-IV), adenosine deaminase (ADA) and lipid peroxidation in obese young and overweight young subjects.ADA, DPP-IV activities and lipid peroxidation were investigated in saliva, as well as insulin, glucose, HbASalivary ADA and DPP-IV activities as well as lipid peroxidation were higher in patients with obesity compared to the normal weight group. Correlations between ADA/DPP-IV activities, lipid peroxidation/ADA activity, ADA activity/hip circumference and BMI/weight were observed.Our results indicate that the increase in the salivary ADA and DPP-IV activities as well as in the lipid peroxidation could be related of the regulation to various aspects of adipose tissue function and inflammatory obesity. It is suggested that these salivary biomarkers may be used as biochemical test in clinical abnormalities present in obesity, in the absence of oral inflammatory diseases.

scholarly journals Increased expression of inactive rhomboid protein 2 in circulating monocytes after acute myocardial infarction

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
P Van Dijck ◽  
C Hannemann ◽  
H Dreger ◽  
K Stangl ◽  
A Ludwig ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Mrna Expression ◽  
Serum Levels ◽  
Necrosis Factor Alpha ◽  
Expression Levels ◽  
National Budget ◽  
Coronary Syndrome ◽  
Tnf Α ◽  
Intermediate Monocytes

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG; Sachbeihilfe HE6092/2) DGK (Deutsche Gesellschaft für Kardiologie) Otto-Hess-Promotionsstipendium Purpose Tumor necrosis factor-alpha (TNF-α) levels in the blood increase in the course of an acute myocardial infarction (AMI) and TNF-α is involved in the impaired recovery of myocardial function following AMI. The interaction of inactive rhomboid protein 2 (iRhom2) with the TNF-α converting enzyme (TACE) is required for the proper shedding of TNF-α from the cell surface of immune cells. We hypothesized, that iRhom2 expression increases in circulating monocytes of patients following AMI.  Methods Circulating monocytes were MACS-sorted from peripheral blood of 50 patients with AMI (NSTEMI, n = 16; STEMI n = 34) at the day of admission (day 1) and 3 days after admission. 50 patients with chronic coronary syndrome (CCS) were recruited as control. mRNA was isolated from sorted monocytes and expression levels of iRhom2, TACE and TNF-α were evaluated by real-time RT-PCR. TNF-α protein levels were assessed in the serum. Levels of circulating classical, intermediate and non-classical monocyte subsets were determined by flow cytometry.  Results There was a significant increase of iRhom2 mRNA expression levels in monocytes (by 14%, p = 0.012), levels of circulating intermediate monocytes (p &lt; 0.001), and TNF-α serum levels (p &lt; 0.001) at day 3 following AMI compared to day 1 reaching levels similar to those observed in CCS patients. In contrast, TNF-α and TACE mRNA expression in circulating monocytes did not differ between day 1 and 3 following AMI. iRhom2 mRNA expression in monocytes on day 3 following AMI correlated with TACE mRNA expression in monocytes (r = 0.72, p &lt; 0.001), TNF-α serum levels (r = 0.33, p = 0.019), and levels of circulating intermediate monocytes (r = 0.37, p = 0.009). Conclusions Following AMI, iRhom2 expression in circulating monocytes increases in parallel to serum levels of TNF-α and levels of circulating intermediate monocytes. These findings suggest that iRhom2 contributes to inflammation following AMI and thus may serve as a potential therapeutic target.

scholarly journals Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases

2020 ◽  
Vol 21 (3) ◽  
pp. 764 ◽  
Author(s):  
Lalita Subedi ◽  
Si Eun Lee ◽  
Syeda Madiha ◽  
Bhakta Prasad Gaire ◽  
Mirim Jin ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Inflammatory Disorder ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Necrosis Factor

Tumor necrosis factor-alpha (TNF-α) is a well-known pro-inflammatory cytokine responsible for the modulation of the immune system. TNF-α plays a critical role in almost every type of inflammatory disorder, including central nervous system (CNS) diseases. Although TNF-α is a well-studied component of inflammatory responses, its functioning in diverse cell types is still unclear. TNF-α functions through its two main receptors: tumor necrosis factor receptor 1 and 2 (TNFR1, TNFR2), also known as p55 and p75, respectively. Normally, the functions of soluble TNF-α-induced TNFR1 activation are reported to be pro-inflammatory and apoptotic. While TNF-α mediated TNFR2 activation has a dual role. Several synthetic drugs used as inhibitors of TNF-α for diverse inflammatory diseases possess serious adverse effects, which make patients and researchers turn their focus toward natural medicines, phytochemicals in particular. Phytochemicals targeting TNF-α can significantly improve disease conditions involving TNF-α with fewer side effects. Here, we reviewed known TNF-α inhibitors, as well as lately studied phytochemicals, with a role in inhibiting TNF-α itself, and TNF-α-mediated signaling in inflammatory diseases focusing mainly on CNS disorders.

A high-throughput screening assay for dipeptidyl peptidase-IV inhibitors using human plasma

2021 ◽  
Author(s):  
Liwei Zou ◽  
Jing Zhang ◽  
Xingkai Qian ◽  
Peifang Song ◽  
Xiaodong Li ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Fluorescence Probe ◽  
Critical Role ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Screening Assay ◽  
Dpp Iv ◽  
High Throughput Screening Assay ◽  
Dipeptidyl Peptidase Iv Inhibitors ◽  
Two Photon Fluorescence

Dipeptidyl peptidase-IV (DPP-IV) plays a critical role in glucose metabolism and has become an important target for type 2 diabetes mellitus. We previously reported a two-photon fluorescence probe glycyl-prolyl-N-butyl-4-amino-1,8-naphthalimide (GP-BAN)...

Dipeptidyl Peptidase IV Inhibitors for Nonalcoholic Fatty Liver Disease – Systematic Review and Metanalysis

2020 ◽  
Vol 16 ◽  
Author(s):  
Lucas Ribeiro dos Santos ◽  
Marcio Luis Duarte ◽  
Maria Stella Peccin ◽  
Antônio Ricardo de Toledo Gagliardi ◽  
Tamara Melnik
Keyword(s):  
Hepatic Steatosis ◽  
Grey Literature ◽  
Specific Treatment ◽  
Reducing Power ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Cochrane Library ◽  
Vast Number ◽  
Dpp Iv ◽  
Dipeptidyl Peptidase Iv Inhibitors

Introduction:: Hepatic steatosis is a frequent condition, that afflicts, especially, obese and insulin resistant patients; diagnosis is made, usually, through imaging tests. Despite the high prevalence and risk of complications, there is no specific treatment approved, though a vast number of medications have been tested. Objective:: To determine the efficacy of dipeptidyl peptidase IV inhibitors (i DPP-IV) in the treatment of NAFLD. Methods:: We searched the electronic databases of the Cochrane Library, MEDLINE, EMBASE and LILACS, as well as reference lists of the included studies and grey literature; 9 studies were selected for inclusion. Results:: 7 studies were used for metanalysis, for 3 outcomes. i DPP-IV showed an ALT-reducing power of MD -10.83 [95% CI 35.23 to 13.57] at 3 months and MD -9.27 [95% CI 10.92 to -7.62] at 6 months of intervention, as well as reduction of hepatic steatosis via MRI of SMD 0.10 [95% CI 0.31 to 0.50]; the overall incidence of adverse events was very low. The studies were considered of low and very low quality by the GRADE evaluation. Conclusion:: Because of the poor overall quality of the studies and heterogeneity of the population analyzed, i DPP-IV did not show efficacy on inflammatory markers or fibrosis in patients with NAFLD.

scholarly journals POS0204 AUTOANTIBODIES AND SYSTEMIC LUPUS ERYTHEMATOSUS INDUCED BY ANTI-TUMOUR NECROSIS FACTOR ALPHA THERAPY IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 318.1-318
Author(s):  
D. Santos Oliveira ◽  
A. Martins ◽  
F. R. Martins ◽  
F. Oliveira Pinheiro ◽  
M. Rato ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Disease Duration ◽  
Seroconversion Rate ◽  
Necrosis Factor Alpha ◽  
Malar Rash ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Over Time

Background:Anti-tumour necrosis factor alpha (anti-TNF-α) therapy is commonly used to treat inflammatory conditions such as rheumatoid arthritis (RA). Autoantibodies namely antinuclear antibodies (ANA) induced by these treatments are well established. However, anti-TNF-α-induced systemic lupus erythematosus (SLE) is rarely described and its incidence is yet unknown.Objectives:This study aimed to determine the prevalence of ANA seroconversion and to characterize the development of SLE induced by anti-TNF-α therapy in patients with RA over time.Methods:An observational retrospective cohort study was conducted with at least one year of follow-up. Patients with diagnosis of RA, according to American College of Rheumatology criteria (ACR), and registered on Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2003 and 2019 were included. Patients with positive ANA (titer ≥100) and/or positive double-strand DNA (dsDNA) antibodies and/or with a diagnosis of SLE at their first visit were excluded. Demographic, clinical and laboratory data were obtained by consulting Reuma.pt. As there are no recognized criteria for drug-induced SLE, the diagnosis of SLE induced by anti-TNF-α was considered if there is a temporal relationship between clinical manifestations and anti-TNF-α-therapy, the presence of at least 1 serologic ACR criteria (ANA or anti-dsDNA) and at least 1 nonserologic ACR criteria (arthritis, serositis, hematologic disorder or malar rash) [1]. Continuous variables are presented with mean, standard deviation, median, quartile 1 and quartile 3. Categorical variables are presented with absolute and relative frequencies.Results:A total of 211 patients (mean age of 49.9±10.9 years old; 84.4% female) were included with a median follow-up time of 6 [3-14] years. We found a seroconversion rate for ANA of 75.4% (n=159) with median treatment duration of 31 [8.5-70.5] months. The most common titre was 1/100 with diffuse and speckled patterns. ANA seroconversion was higher for etanercept (47.8%, n=76) than with adalimumab (23.9%, n=38), infliximab (13.8%, n=22), golimumab (12.6%, n=20) or certolizumab (1.9%, n=3). SLE induced by anti-TNF-α occurred in two patients (0.9%) with erosive and seropositive (rheumatoid factor and anti-citrullinated protein antibodies) RA previously treated with two conventional synthetic disease-modifying antirheumatic drugs, including methotrexate. The first patient, a female with 66 years old and 17 years of disease duration, developed SLE after 16 months of infliximab, with constitutional symptoms, abrupt worsening of polyarthritis, ANA titer of 1/320 diffuse pattern and positive dsDNA (248 UI/mL) antibodies. The second patient, a woman with 43 years old and 11 years of disease duration, developed SLE after 41 months of adalimumab with malar rash and ANA titer of 1/320 diffuse pattern, positive dsDNA (285 UI/mL), positive anti-histone antibodies and hypocomplementemia. In these two cases, anti-TNF-α therapy was stopped and recovery was spontaneous without treatment. The first patient switched to adalimumab and the second switched to golimumab without recurrence of SLE for more than ten years.Conclusion:We found a high rate of ANA seroconversion induced by anti-TNFα therapy in patients with RA. However, similar to previous literature, only 0.9% of patients developed SLE with mild manifestations without major organ involvement. Although the drug with the highest ANA seroconversion rate was etanercept, those responsible for induced SLE were infliximab and adalimumab. Patients improved after discontinuation of therapy and tolerated an alternative anti-TNF-α drug without recurrence of induced SLE over time. Therefore, ANA and SLE induced by anti-TNF-α should be considered and reported in the follow-up of RA patients. Further research is needed to explore the impact of this adverse event on the outcomes of treatment over time.References:[1]Hochberg MC. Arthritis Rheum. 1997;40(9):1725.Disclosure of Interests:None declared

Alterations of serum levels of plasminogen, TNF-α, and IDO in granulomatosis with polyangiitis patients

Vascular ◽  
2021 ◽  
pp. 170853812098630
Author(s):  
Dobroslav Kyurkchiev ◽  
Tsvetelina Yoneva ◽  
Adelina Yordanova ◽  
Ekaterina Kurteva ◽  
Georgi Vasilev ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Necrosis Factor Alpha ◽  
Cross Sectional ◽  
Spearman's Rho ◽  
Tnf Α ◽  
Spearman’S Rho

Background Granulomatosis with polyangiitis (GPA) is a representative of vasculitides associated with anti-neutrophil cytoplasmic autoantibodies. “Classical” antibodies directed against proteinase 3 are involved in the pathogenesis and are part of the GPA diagnosis at the same time. Along with them, however, antibodies against Lysosomal-Associated Membrane Protein-2 (LAMP-2) and antibodies directed against plasminogen have been described in GPA. Objectives and methodology: We performed a cross-sectional study enrolling 34 patients diagnosed with GPA. Our study was aimed at looking for correlations between serum levels of LAMP-2 and plasminogen and the clinical manifestations of the GPA. Furthermore, we examined serum levels of tumor necrosis factor-alpha (TNF-α) and its associated indoleamine-pyrrole 2,3-dioxygenase (IDO), as well as we looked for a correlation between these cytokines and the clinical manifestations of GPA. Results The results showed that in GPA, serum plasminogen levels were negatively associated with renal involvement (receiver operating characteristic (ROC) area under the curve (AUC) of 0.78) (95% CI 0.53–0.91), p = 0.035, and the extent of proteinuria, Spearman’s Rho = –0.4, p = 0.015. Increased levels of TNF-α and IDO correlated with disease activity, Spearman’s Rho =0.62, p = 0.001 and Spearman’s Rho = 0.4, p = 0.022, respectively, whereas only TNF-α was increased in severe forms of GPA with lung involvement (ROC AUC of 0.8) (95% CI 0.66–0.94), p = 0.005. Conclusions In this study, we demonstrate the alteration of soluble factors, which play an important role in the pathogenesis of GPA and their relationship with the clinical manifestations of the disease. Our main results confirm the associations of increased secretory TNF-α and some clinical manifestations, and we describe for the first time decreased serum plasminogen levels and their association with renal involvement.

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