Genetic variants of interferon-gamma and its mRNA expression and inflammatory parameters in the pathogenesis of vitiligo

2017 ◽  
Vol 95 (4) ◽  
pp. 474-481 ◽  
Author(s):  
Rehab A. Karam ◽  
Haidy E. Zidan ◽  
Mohamed H. Khater

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.

2019 ◽  
Vol 64 (11) ◽  
pp. 673-676
Author(s):  
Asmaya Saftar Huseynova

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.


2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Amal Ahmed Mohamed ◽  
Wafaa Gh. Shousha ◽  
Moushira Erfan Zaki ◽  
Hala T. El-Bassyouni ◽  
Hadeel El-Hanafi ◽  
...  

Abstract Background: Obesity is an alarming threat to health in Egypt. More than one in three Egyptians is obese, the highest rate in the world. We aimed to delineate the variability of inflammation and endothelial dysfunction markers among Egyptian females with different obesity classes. Methods: Out of 130 females, 70 were categorized into three obesity groups: Class I, body mass index (BMI) 30–34.9 kg/m2; Class II, BMI 35–39.9 kg/m2 and Class III BMI ≥ 40 kg/m2, besides 60 control subjects. Anthropometric measurements were recorded and serum levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin (IL) 6 (IL-6), IL-12, soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1) were assessed among participants. Results: In all three classes of obesity, significant increase (P <0.05) in BMI, waist-hip ratio, fat mass and body fat mass % were noted. CRP and sVCAM-1 levels were increased among the three obesity groups. TNF-α levels were increased in class II and III obesity groups. IL-6 and IL-12 levels were elevated in class I and class III groups. While, ICAM-1 levels were increased in class III obesity group. Conclusion: Based on individuals’ BMI, serum levels of TNF-α, CRP, IL-6, IL-12, sVCAM-1 and sICAM-1 are differentially altered with the progression of obesity. We strongly support the hypothesis that, as the obesity rate is still mounting, a subclinical inflammatory reaction has a role in pathogenesis of obesity and emphasize the elevation of endothelial dysfunction in individuals with obesity.


1998 ◽  
Vol 5 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Ulrich Sack ◽  
Ullrich Burkhardt ◽  
Michael Borte ◽  
Hiltrud Schädlich ◽  
Kerstin Berg ◽  
...  

ABSTRACT Serum cytokine levels were measured in 275 healthy children of different ages (3 to 17 years). Interleukin-1 receptor antagonist (IL-1RA), soluble IL-2R (sIL-2R) (sCD25), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), soluble TNF receptor type II (sTNF-RII) (sCD120b), gamma interferon (IFN-γ), soluble intercellular adhesion molecule 1 (sICAM-1) (sCD54), soluble E selectin (sE-selectin) (ELAM-1; sCD62E), sCD14, and neopterin were measured with commercial test kits. The mean levels of IL-1RA, sIL-2R, TNF-α, sICAM-1, sE-selectin, and sCD14 were higher than in healthy adults. In contrast, IFN-γ and IL-8 were hardly detectable in children and thereby significantly lower than in adults. In the case of TNF-α, sICAM-1, sE selectin, and sCD14, there was a high interindividual variability, apparently unrelated to disease. The profiles of some cytokines, i.e., IL-1RA, IL-6, and TNF-α, showed age-related increases that overlapped with known patterns of physical growth. Of note, sIL-2R and sE-selectin instead declined with time. Because of the remarkable age-dependent variability in healthy pediatric subjects, disease-related changes, as well as therapy-dependent alterations, should be considered with caution.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 947
Author(s):  
Mab P. Corrêa ◽  
Libnah L. Areias ◽  
Rebeca D. Correia-Silva ◽  
Solange C. G. P. D’Ávila ◽  
Andréia M. Leopoldino ◽  
...  

Galectin-9 (Gal-9) is a beta-galactoside-binding protein with a variety of biological functions related to immune response. However, in allergic diseases, its mechanism of action is not fully understood. This study evaluates the expression pattern of Gal-9 in patients with atopic dermatitis (AD), in ovalbumin (OVA)-induced experimental atopic dermatitis (AD) in mice, as well as its effect on human keratinocytes. The skin of OVA-immunized BALB/c mice was challenged with drops containing OVA on days 11, 14–18, and 21–24. HaCaT cells were cultured in the following experimental conditions: control (growth medium only) or stimulated with TNF-α/IFN-γ, or IL-4, or IL-17 with or without Gal-9 treatment. AD was characterized by increased levels of Gal-9 in mouse and human skin, especially in the epidermis, and with a marked influx of Gal-9 positive eosinophils and mast cells compared to the control group. Gal-9 showed an immunomodulatory effect on keratinocytes by decreasing the release of IL-6 by IL-4-stimulated keratinocytes or increasing the IL-6 and RANTES levels by IL-17- or TNF-α/IFN-γ-stimulated cells, respectively. Under IL-17, Gal-9 treatment also altered the proliferation rate of cells. Overall, increased levels of Gal-9 in AD skin contribute to the control of inflammatory response and the proliferative process of keratinocytes, suggesting this lectin as a relevant therapeutic target.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Nearmeen M. Rashad ◽  
Amal S. El-Shal ◽  
Hala G. Abomandour ◽  
Amr Mostafa Kamel Aboelfath ◽  
Mohamed el sayed Rafeek ◽  
...  

Abstract Background Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance. Intercellular adhesion molecule-1 (ICAM-1) is a proinflammatory and proatherogenic cytokine which is associated with atherosclerosis, insulin resistance, and cardiovascular disease (CVD). The pathogenesis of PCOS is not precisely known. Thus, the purpose of this study was to investigate the potential role of ICAM-1 expression and serum ICAM-1 concentrations in pathogenesis of PCOS. Moreover, we aimed to evaluate the possible relationship between ICAM-1 gene expression with carotid intima-media thickness as well as clinic-morphological features of PCOS. Methods This case control study enrolled 180 patients with PCOS and 120 controls groups and they were stratified according to their fasting plasma glucose (FPG) into three subgroups; normal glucose tolerance (NGT) [n = 75], those with impaired glucose tolerance (IGT) [n = 65], and 40 patients with type 2 diabetes mellitus (T2DM). Circulating ICAM-1 expression levels were determined by real time polymerase chain reaction (RT-PCR). Serum ICAM-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Results Our results revealed that PCOS patients had higher values of ICAM-1expression and serum levels. Among PCOS patients, T2DM patients had the highest values of ICAM-1 expression and serum levels compared to IGT and NGT subgroups. The ICAM-1 expression and serum levels were significantly positive correlated with cardiovascular risk and PCOS phenotypes. Linear regression test showed that HOMA-IR was the main predictors of serum ICAM-1 levels in PCOS. Receiver operating characteristic curve (ROC) analysis revealed that, the power of ICAM-1 expression levels was higher than serum ICAM-1 in diagnosis of PCOS and in differentiating T2DM from IGT and NGT subgroups. Interestingly, combination of both ICAM-1 expression and serum levels improved the diagnostic role of serum ICAM-1. Conclusion ICAM-1 expression and serum levels were higher in women with PCOS compared to control group also, there was a strong independent association between higher ICAM-1 expression and serum levels with cardiovascular risks in PCOS group.


2020 ◽  
Vol 12 (1) ◽  
pp. 40-4
Author(s):  
Ismawati Ismawati ◽  
Enikarmila Asni ◽  
Mukhyarjon Mukhyarjon ◽  
Ilhami Romus

BACKGROUND: Diabetes mellitus (DM) is associated with an accelerated atherosclerotic macrovascular disease affecting medium-sized arteries. Several evidences support the role of oxidative stress in atherogenesis. However, the role of alpha lipoic acid (ALA) to prevent atherosclerosis is still debatable. This study was conducted to determine the effect of 60 mg/kg/day ALA for 21 days toward the expression of intercellular adhesion molecule-1 (ICAM-1) in rat model.METHODS: Eighteen male rats were divided into three groups labelled as control group, type 2 DM (T2DM) group, and T2DM+ALA group. The T2DM rat models were created by intraperitoneally injecting 50 mg/kg streptozotocin, followed by 110 mg/kg nicotinamide. Immunohistochemistry was used to evaluate the ICAM- 1 expression in rats. Quantitative image analysis of immunohistochemical stains was done on the abdominal aorta using Adobe Photoshop CS3 to find the area percentage and intensity. Kruskal-Wallis and Mann-Whitney tests were used to compare the mean value of area percentage and intensity.RESULTS: There was an increase in area percentage and intensity of ICAM-1 expression. The highest area percentage of ICAM-1 expression was found in the DM group, while the lowest was found in the control group. There were significant differences in the area percentage and intensity between DM+ALA group and DM group, where the area percentage and intensity of ICAM-I in DM group was higher than the DM+ALA group.CONCLUSION: In conclusion, our results demonstrate that ALA inhibits the expression of ICAM-1 in T2DM rat models.KEYWORDS: atherosclerosis, ICAM-1, alpha lipoic acid


2019 ◽  
Vol 40 (5) ◽  
pp. 1117-1131 ◽  
Author(s):  
Tsubasa Takizawa ◽  
Tao Qin ◽  
Andreia Lopes de Morais ◽  
Kazutaka Sugimoto ◽  
Joon Yong Chung ◽  
...  

Cortical spreading depolarization (CSD) induces pro-inflammatory gene expression in brain tissue. However, previous studies assessing the relationship between CSD and inflammation have used invasive methods that directly trigger inflammation. To eliminate the injury confounder, we induced CSDs non-invasively through intact skull using optogenetics in Thy1-channelrhodopsin-2 transgenic mice. We corroborated our findings by minimally invasive KCl-induced CSDs through thinned skull. Six CSDs induced over 1 h dramatically increased cortical interleukin-1β (IL-1β), chemokine (C-C motif) ligand 2 (CCL2), and tumor necrosis factor-α (TNF-α) mRNA expression peaking around 1, 2 and 4 h, respectively. Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were only modestly elevated. A single CSD also increased IL-1β, CCL2, and TNF-α, and revealed an ultra-early IL-1β response within 10 min. The response was blunted in IL-1 receptor-1 knockout mice, implicating IL-1β as an upstream mediator, and suppressed by dexamethasone, but not ibuprofen. CSD did not alter systemic inflammatory indices. In summary, this is the first report of pro-inflammatory gene expression after non-invasively induced CSDs. Altogether, our data provide novel insights into the role of CSD-induced neuroinflammation in migraine headache pathogenesis and have implications for the inflammatory processes in acute brain injury where numerous CSDs occur for days.


2017 ◽  
Vol 96 (2) ◽  
pp. 65-68 ◽  
Author(s):  
Murad Mutlu ◽  
Erkan Vuralkan ◽  
Istemihan Akin ◽  
Hikmet Firat ◽  
Sadik Ardic ◽  
...  

The aim of the current study was to compare the changes in polysomnographic indices and serum levels of C-reactive protein (CRP), cystatin C, tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in patients with obstructive sleep apnea (OSA) who were treated surgically via a uvulopalatal flap (UPF) technique. Twenty-five patients (14 men, 11 women), average age 46.2 ± 9.3 years, who underwent UPF surgery were included in this study. Serum biochemical analyses and polysomnographic examinations were performed before and 6 months after the surgery. Pre- and postoperative values of apnea hypopnea index (AHI), oxygen desaturation index (ODI), and minimum oxygen concentrations, as well as serum levels of CRP, cystatin C, TNF-α, and ICAM-1 were compared. Comparison of variables before and after UPF surgery demonstrated that AHI (p = 0.001), ODI (p < 0.001) and oxygen saturation (p < 0.001) were significantly improved. In addition, serum levels of CRP (p = 0.036), cystatin C (p = 0.005), TNF-α (p < 0.001), and ICAM-1 (p < 0.001) were significantly reduced 6 months after surgery. Our results suggest that UPF is an effective surgical method that alleviates the severity of OSA. Moreover, it may have the potential to prevent the development of atherosclerosis by attenuating the inflammatory process induced by activation of inflammatory mediators such as CRP, TNF-α, ICAM-1, and cystatin C.


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