scholarly journals Identification of Peptides as Novel Inhibitors to Target IFN-γ, IL-3, and TNF-α in Systemic Lupus Erythematosus

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Ghulam Mustafa ◽  
Hafiza Salaha Mahrosh ◽  
Mahwish Salman ◽  
Sumaira Sharif ◽  
Raheela Jabeen ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Protein Docking ◽  
Ligand Docking ◽  
Drug Candidate ◽  
Systemic Lupus ◽  
Binding Interactions ◽  
Tnf Α ◽  
Ifn Γ

Autoimmune disorder is a chronic immune imbalance which is developed through a series of pathways. The defect in B cells, T cells, and lack of self-tolerance has been greatly associated with the onset of many types of autoimmune complications including rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and chronic inflammatory demyelinating polyneuropathy. The SLE is an autoimmune disease with a common type of lupus that causes tissue and organ damage due to the wide spread of inflammation. In the current study, twenty anti-inflammatory peptides derived from plant and animal sources were docked as ligands or peptides counter to proinflammatory cytokines. Interferon gamma (IFN-γ), interleukin 3 (IL-3), and tumor necrosis factor alpha (TNF-α) were targeted in this study as these are involved in the pathogenesis of SLE in many clinical studies. Two docking approaches (i.e., protein-ligand docking and peptide-protein docking) were employed in this study using Molecular Operating Environment (MOE) software and HADDOCK web server, respectively. Amongst docked twenty peptides, the peptide DEDTQAMMPFR with S -score of -11.3018 and HADDOCK score of − 10.3 ± 2.5  kcal/mol showed the best binding interactions and energy validation with active amino acids of IFN-γ protein in both docking approaches. Depending upon these results, this peptide could be used as a potential drug candidate to target IFN-γ, IL-3, and TNF-α proteins to control inflammatory events. Other peptides (i.e., QEPQESQQ and FRDEHKK) also revealed good binding affinity with IFN-γ with S -scores of -10.98 and -10.55, respectively. Similarly, the peptides KHDRGDEF, FRDEHKK, and QEPQESQQ showed best binding interactions with IL-3 with S -scores of -8.81, -8.64, and -8.17, respectively.

scholarly journals Correlations of Expression Levels of a Panel of Genes (IRF5, STAT4, TNFSF4, MECP2, and TLR7) and Cytokine Levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, and TNF-α) with Systemic Lupus Erythematosus Outcomes in Jordanian Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Amal H. Uzrail ◽  
Areej M. Assaf ◽  
Shtaywy S. Abdalla
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Renal Damage ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Expression Levels ◽  
Cardiovascular Damage ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ

Systemic lupus erythematosus (SLE) is characterized by systemic end-organ damage. We investigated the involvement of IRF5, TLR-7, MECP2, STAT4, and TNFSF4 genes and TNF-α, IFN-γ, IL-2, IL-12, IL-6, and IL-10 cytokines in SLE pathogenesis and in organ damage in Jordanian patients. Blood was collected from 51 patients and 50 controls. Expression levels of SLE genes in PBMCs and cytokine levels were determined using RT-PCR and ELISA, respectively. Expression levels of all genes and levels of TNF-α, IL-12, IL-6, and IL-10 were higher in SLE patients than those in controls (p<0.05), whereas IL-2 level was lower. High STAT4 (α), TNFSF4, and IL-10 levels correlated with cardiovascular damage, and high MECP2 (α) and TNF-α correlated with renal damage. Pulmonary and musculoskeletal damages correlated with high levels of TNFSF4. We concluded that STAT4 and TNFSF4 genes with TNF-α and IL-10 cytokines could be used as biomarkers to assess SLE activity and manage treatment.

SAT0205 A MORE SPECIFIC INTEGRATED MODEL FOR IDENTIFYING BACTERIAL INFECTION IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1045-1046
Author(s):  
M. Feng ◽  
X. C. Zhao ◽  
J. Luo
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Bacterial Infection ◽  
Disease Activity ◽  
Sensitivity And Specificity ◽  
Lupus Erythematosus ◽  
Roc Curves ◽  
Systemic Lupus ◽  
Routine Examination ◽  
Tnf Α ◽  
Ifn Γ

Background:Systemic lupus erythematosus (SLE) is a multisystemic inflammatory disorder [1]. Given that immunosuppressive therapy is adopted as the predominant treatment option for SLE, up to half of SLE patients develop infections during their disease progress, and bacterial infection serves as the leading cause of morbidity and mortality in SLE patients [2]. Owing to the therapeutic regimen to bacterial infection and SLE flare are absolutely opposite, timely diagnosis and correct treatment are of vital importance, and improper treatment strategy may be fatal. No single biomarker, however, has exhibited sufficient sensitivity and specificity to serve as a standard tool for distinguishing bacterial infection from SLE flare.Objectives:To find a method by integrating cytokines, lymphocyte cells and routine examination biomarkers to observe its capacity for identifying bacterially infected SLE patients.Methods:Total 175 SLE patients (65 infected and 110 flare) were recruited into our study. The criteria of bacterial infection was positive isolation of bacteria, typical clinical symptoms and signs, imaging positive results and positive feedback on antibacterial treatment and lupus flare was regarded as three points higher than their previous SLEDAI. The disease activity of SLE patients was evaluated based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Lymphocyte cells (CD3+T, CD4+T, CD8+T, B, NK, Th1, Th2, Th17 and Treg) and cytokines [interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-17] were measured by flow cytometry. Blood routine examination, erythrocyte sedimentation rate (ESR), C-Reactive Protein (CRP) Complement 3 (C3), C4, procalcitonin (PCT), immunoglobulin M (IgM), IgA and IgG were also evaluated. Partial least square discriminant analysis (PLS-DA) and supervised orthogonal PLS-DA (OPLS-DA) were applied to perform multivariate analysis of the data and further group the patients with bacterial infection. Receiver operating characteristic (ROC) curves were also plotted to investigate the ability of individual indicator and the combination of multiple indicators to identify bacterial infection.Results:The PLS-DA model showed a clear identification effect by the performance of R2Y=0.991 and Q2=0.970. The OPLS-DA model (R2Y=0.996 and Q2=0.991) exhibited a better separation of patients with bacterial infection. And the Observed vs. predicted plot of the OPLS-DA model demonstrated that all SLE patients were correctly separated into infected or flare groups, indicating that the model had a strong predictive ability for bacterial infection. For single indicator, infected patients had higher WBC, neutrophil (NEUT), ESR, CRP and PCT (P=0.002, 0.019, 0.002, <0.001, <0.001, respectively), and lower Treg cells (P=0.012). The levels of serum IL-6, IL-10, IFN-γ and TNF-α (P<0.001, =0.022, 0.014, 0.011, respectively) were significantly increased in infected group. ROC curves showed that the combination of the ten indicators showed the largest AUC and the highest accuracy, as well as balanced and relatively high sensitivity and specificity. Furthermore, the AUC of the combination was greatly higher than that of WBC, NEUT, ESR, CRP, PCT, Treg, IL-6, IL-10, IFN-γ and TNF-α (P<0.001).Conclusion:PLS-DA, OPLS-DA models including cytokines, lymphocyte cells and routine biomarkers and combination of WBC, NEUT, ESR, CRP, PCT, Treg, IL-6, IL-10, IFN-γ and TNF-α in ROC curve may be more predictive for finding bacterial infection in SLE and may prompt clinicians more promptly and accurately to help them make correct medication.References:[1]Illescas-Montes R, Corona-Castro CC, Melguizo-Rodríguez L, et al. Infectious processes and systemic lupus erythematosus. Immunology 2019;158:153-160.[2]Furst DE, Breedveld FC, Kalden JR, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases. Ann Rheum Dis 2002; 61: ii2–7.Disclosure of Interests:None declared

Gene expression of cytokines (TNF-α, IFN-γ), serum profiles of IL-17 and IL-23 in paediatric systemic lupus erythematosus

Lupus ◽  
2012 ◽  
Vol 21 (10) ◽  
pp. 1105-1112 ◽  
Author(s):  
A Rana ◽  
RW Minz ◽  
R Aggarwal ◽  
S Anand ◽  
N Pasricha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Tnf Α ◽  
Ifn Γ

scholarly journals IL-2, IL-5, TNF-α and IFN-γ mRNA expression in epidermal keratinocytes of systemic lupus erythematosus skin lesions

Clinics ◽  
2011 ◽  
Vol 66 (1) ◽  
pp. 77-82 ◽  
Author(s):  
José Ronaldo M Carneiro ◽  
Hellen T Fuzii ◽  
Cristiane Kayser ◽  
Fernando L Alberto ◽  
Fernando A Soares ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mrna Expression ◽  
Lupus Erythematosus ◽  
Skin Lesions ◽  
Epidermal Keratinocytes ◽  
Systemic Lupus ◽  
Tnf Α ◽  
Ifn Γ

scholarly journals The Plasma Interleukin (IL)-35 Level and Frequency of Circulating IL-35+ Regulatory B Cells are Decreased in a Cohort of Chinese Patients with New-onset Systemic Lupus Erythematosus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhuang Ye ◽  
Yanfang Jiang ◽  
Dejun Sun ◽  
Wei Zhong ◽  
Ling Zhao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Chinese Patients ◽  
Regulatory B Cells ◽  
Systemic Lupus ◽  
Total Blood ◽  
Tnf Α ◽  
Ifn Γ

Abstract Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that is associated with the destruction of immune tolerance and activation of B cells. Interleukin (IL)-35 and IL-35-producing (IL-35+) regulatory B cells (Bregs) have been demonstrated to possess immunosuppressive functions, but their roles in the initiation and early development of SLE have not been explored. Here, we measured and compared the frequencies of blood regulatory B cell subsets and the concentrations of plasma IL-35, IL-10, IL-17A, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in 47 Chinese patients with newly diagnosed SLE and 20 matched healthy controls (HCs). The SLE patients had decreased percentages of IL-35+ B cells and IL-10+ B cells among the total blood B cells as well as decreased concentrations of plasma IL-35. In addition, higher levels of plasma IL-10, IFN-γ, TNF-α, and IL-17 along with higher frequencies of circulating plasma and memory B cells were observed in the SLE patients. The percentage of IL-35+ Bregs and the serum IL-35 level were inversely correlated with the SLE disease activity index and the erythrocyte sedimentation rate (ESR) levels. Our results indicate that IL-35+ Bregs and IL-35 may play protective roles in SLE initiation and progression.

scholarly journals Serum Levels and in Vitro Production of Th1- and Th2-Type Cytokines by Peripheral Blood Mononuclear Cells in Patients Suffering from Systemic Lupus Erythematosus

2010 ◽  
Vol 29 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Vidosava Đorđević ◽  
Lilika Zvezdanović ◽  
Vladan Ćosić ◽  
Predrag Vlahović ◽  
Slavica Kundalić ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Peripheral Blood Mononuclear Cells ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Serum Levels ◽  
Systemic Lupus ◽  
Con A ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Ifn Γ

Serum Levels and in Vitro Production of Th1- and Th2-Type Cytokines by Peripheral Blood Mononuclear Cells in Patients Suffering from Systemic Lupus ErythematosusTh1-type and Th2-type cytokine profiles and adhesion molecules in the serum of patients suffering from systemic lupus erythematosus and the cytokine production by peripheral blood mononuclear cells (PBMC) were studied. Tumor necrosis factor-alpha (TNF-α), interferongamma (IFN-γ), interleukin-1β (IL-1β), IL-4, IL-10, IL-13, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured using ELISA technique in the sera of 16 systemic lupus erythematosus patients without vasculitis (SLE), 30 SLE patients with vasculitis (LV), and in 18 healthy controls. The cytokines were also measured in the culture media of unstimulated, concana valin-A (Con-A) and phorbol-12-myristate-13-acetate (PMA) stimulated PBMC. TNF-α serum levels were significantly elevated in both SLE and LV patients and those of IL-1β in SLE patients. TNF-α was also significantly increased in SLE compared to LV patients. Serum levels of all three Th-2 cytokines were significantly elevated in both SLE and LV patients compared to healthy controls. Serum IFN-γ and Th2 cytokine levels were significantly increased in patients with more active disease. Both ICAM-1 and VCAM-1 were significantly increased in SLE patients and only VCAM-1 in LV patients. ICAM-1 showed a significant correlation with IL-1β, IFN-γ, IL-4 and IL-10 in both patient groups. In the SLE group VCAM-1 correlated significantly only with ICAM-1, but in the LV group only with IL-1β and IFN-γ. Compared to healthy controls, basal TNF-α and IL-4 production by unstimulated PBMC derived from SLE patients were significantly increased. Con-A-stimulated PBMC of both SLE groups produced significantly more IFN-γ, IL-4 and IL-13 than Con-A-stimulated control cells. Con-A-stimulated cells derived from LV patients produced much more INF-γ than cells from SLE patients. PMA strongly stimulated INFγ, TNFα and IL-13 production by cells derived from both SLE groups but had no effect on IL-4 production. In addition, it had little if any effect on the production of INFγ and IL-13 by PBMC derived from healthy donors. These findings suggest that the altered pattern of cytokine production by PBMC may play an important role in the SLE pathophysiology, accounting for differences in the clinical expression of the disease. The differences in adhesion molecules production and their correlation with cytokines suggest ICAM-1 and VCAM-1 as useful markers in SLE patients stratification.

Expression of High Mobility Group Box Chromosomal Protein 1 and Its Modulating Effects on Downstream Cytokines in Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (4) ◽  
pp. 766-775 ◽  
Author(s):  
JIE LI ◽  
HONGFU XIE ◽  
TING WEN ◽  
HONGBO LIU ◽  
WU ZHU ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Messenger Rna ◽  
Activity Index ◽  
High Mobility ◽  
High Mobility Group ◽  
Chromosomal Protein ◽  
Systemic Lupus ◽  
Tnf Α

Objective.To compare the expression of high mobility group box chromosomal protein 1 (HMGB1) and the modulating effects on its downstream cytokines in patients with systemic lupus erythematosus (SLE) and healthy controls.Methods.HMGB1 concentrations in serum from SLE patients and controls were measured by immunoblot analysis. HMGB1 messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMC) was detected by real-time reverse transcription–polymerase chain reaction. Immunofluorescence assay was employed to examine the translocation of HMGB1 in monocytes after endotoxin stimulation. Release of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) by PBMC after rHMGB1 stimulation was also measured.Results.Serum HMGB1 levels and HMGB1 mRNA expressions in PBMC were elevated in SLE patients compared with controls. A positive correlation was demonstrated between HMGB1 concentrations and SLE Disease Activity Index. There was an inverse correlation between HMGB1 levels and C4 and C3 concentrations in SLE patients. HMGB1 concentrations were higher in patients with vasculitis and myositis. Lipopolysaccharide stimulated a temporarily elevated release of HMGB1 in SLE patients compared with controls. The pattern and localization of HMGB1 staining in monocytes were similar in both groups. After stimulation with rHMGB1, TNF-α level decreased but IL-6 level increased in SLE patients compared with controls.Conclusion.Our findings suggest that increased serum levels of HMGB1 in SLE may be associated with lupus disease activity. The altered production of TNF-α and IL-6 in response to rHMGB1 stimulation may participate in the disruption of cytokine homeostasis in SLE.

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