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Immunological Investigations
Marcel Dekker
Immunological Investigations

Marcel Dekker

0882-0139

Immunological Investigations/Journal Immunological InvestigationsSCIISTP
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    Tetrandrine Attenuates Cartilage Degeneration, Osteoclast Proliferation, and Macrophage Transformation through Inhibiting P65 Phosphorylation in Ovariectomy-induced Osteoporosis

    Shi, FangNi, LeiGao, Ye-Mei
    15页
    查看更多>>摘要：Background Osteoporosis is a common metabolic bone disease with high prevalence. Tetrandrine (TET) suppressed osteoclastogenesis, while the roles of TET in osteoporosis regulation remained unclear. Thus, the study aimed to investigate the effect of TET on osteoporosis and the underlying mechanism. Methods The osteoporosis rabbit model was established through anterior cruciate ligament transection (ACLT) and bilateral ovariectomy (OVX). The degeneration of articular cartilage was assessed using HE staining and Alcian blue staining. The liver and kidney tissue injury was determined using HE staining. The activity of osteoclasts was evaluated using Tartrate-resistant acid phosphatase (TRAP) staining. The changes in bone structural parameters were determined through measuring the BMD, BV/TV, Tb.Th, Tb.N, and Tb.Sp, and the serum levels of calcium and phosphorus. Macrophage polarization was determined using Flow cytometry. Results The bone structural parameters including BMD, BV/TV, Tb.N, Tb.Th and Tb.Sp were changed in osteoporosis rabbit, which was reversed by TET. Besides, TET suppressed the increased serum levels of calcium and phosphorus in osteoporosis rabbit. Furthermore, TET inhibited the degeneration of articular cartilage and the activity of osteoclasts induced by osteoporosis. Moreover, TET inhibited the levels of MMP-9, PPAR-gamma, RANKL, beta-CTX and TRACP-5b, and increased the levels of OPG, ALP and osteocalcin (OC) in osteoporosis. Additionally, TET promoted macrophage transformation from M1 to M2 in osteoporotic and inhibited the production of IL-1 beta, TNF-alpha, and IL-6. TET also inhibited the p65 phosphorylation in osteoporosis. Besides, TET reversed RANKL-induced osteoclasts proliferation, p65 phosphorylation, and the expression changes of RANKL, Ki67, PPAR-gamma, ALP, OPG. Conclusion TET attenuated bone structural parameters including BMD, BV/TV, Tb.N, Tb.Th and Tb.Sp, inhibited articular cartilage degeneration, promoted bone formation, inhibited the inflammatory response, and promoted macrophage transformation from M1 to M2 via NF-kappa B inactivation in osteoporosis. TET may be a promising drug for osteoporosis therapy.
      原文链接:
    • NSTL
    • Taylor & Francis

    Assessment of the Relationship between Clinical Variants of Psoriasis and Killer Immunoglobulin-like Receptor (KIR) Genes: A Systematic Review with Meta-analysis

    Macias-Barragan, JoseMontoya-Buelna, MargaritaEnciso-Vargas, MoisesAlvarado-Ruiz, Liliana...
    16页
    查看更多>>摘要：Background Psoriasis (Ps) is an autoimmune dermatosis. Previous studies have shown an association between KIR genes and susceptibility to some clinical variants of Ps. Therefore, we conducted an exhaustive systematic review with meta-analysis to evaluate the relationship between KIR genes and susceptibility to clinical variants of Ps in the overall population and according to ethnicity. Methods According to PRISMA guidelines, we performed a systematic review through PubMed and Web of Science to identify relevant available scientific publications about KIR genes and Ps. The quality of the studies was evaluated using the Newcastle-Ottawa scale. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using random and fixed effect models for the analyzed genes. Heterogeneity was tested using Cochran's Q-Statistic and I-2, and the risk of bias was tested using the Begg test and Egger linear regression. Results A total of 10 case-control studies were included, comprising a variable number of KIR typified genes and psoriasis vulgaris (PsV) as the main clinical variant studied. In the total pooled results, the KIR2DS1 gene (OR = 1.518, p = .010, 95%CI: 1.105 to 2.086) was related to higher susceptibility to PsV, while the KIR2DS4 (OR = 0.563, p = .005, 95%CI: 0.376 to 0.842) and KIR3DL1 (OR = 0.602, p = .040, 95%CI: 0.370 to 0.977) genes were related to protection against PsV. Conclusion This meta-analysis demonstrates that subjects that carry the KIR2DS1 gene could have a potential risk factor for the development of PsV. Conversely, KIR2DS4 and 3DL1 genes appear to confer protection against PsV.
      原文链接:
    • NSTL
    • Taylor & Francis

    MiR-135b Alleviates Airway Inflammation in Asthmatic Children and Experimental Mice with Asthma via Regulating CXCL12

    Liu, YingHuo, Shi-GuangXu, LingChe, Yuan-Yuan...
    15页
    查看更多>>摘要：Objective To clarify the possible influence of miR-135b on CXCL12 and airway inflammation in children and experimental mice with asthma. Methods The expressions of miR-135b and CXCL12 were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in the serum of asthmatic children. Besides, the experimental asthmatic mice were established by aerosol inhalation of ovalbumin (OVA) followed by the treatment with agomiR-135b and antagomir-135b. Pathological changes of lung tissues were observed via HE staining and PAS staining. Besides, the airway hyperresponsiveness of mice was elevated and bronchoalveolar lavage fluid (BALF) was isolated for cell categorization and counting. The inflammatory cytokines in BALF were determined by enzyme-linked immunosorbent assay (ELISA), and the infiltration of Th17 cells in lung tissues was measured using flow cytometry. Results MiR-135b was downregulated and CXCL12 was upregulated in asthmatic children and mice. Overexpression of miR-135b may down-regulate CXCL12 expression in the lung of OVA mice, resulting in significant decreases in inflammatory infiltration, hyperplasia of goblet cell, airway hyperresponsiveness, cell quantity, as well as the quantity of eosinophilic granulocytes, neutrophils and lymphocytes in BALF. Also, the levels of inflammatory cytokines (IL-4, IL-5, IL-13 and IL-17) and the ratio of Th17 cells and IL-17 levels in lung tissues were decreased. However, miR-135b downregulation reversed these changes in OVA mice. Conclusion MiR-135b may inhibit immune responses of Th17 cells to alleviate airway inflammation and hyperresponsiveness in asthma possibly by targeting CXCL12, showing the potential value in asthma treatment.
      原文链接:
    • NSTL
    • Taylor & Francis

    Association of Polymorphism in IL-18 Gene with Periodontitis in Uyghur Adults in Xinjiang and Evidence from Six Case-Control Studies with a Comprehensive Analysis

    Shan, ChaoMa, TingWang, Ting TingWu, Long...
    20页
    查看更多>>摘要：Aim The aim of the study was to evaluate the association of IL-18 137 G > C, 607 C > A gene polymorphism in Uyghur population with chronic periodontitis (CP) and combine the results with the meta-analysis Methods In a case-control study, 200 cases with CP and 100 healthy controls were recruited; IL-18 137 G > C, 607 C > A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In the meta-analysis, we used electronic databases, including CNKI, Wan Fang, PubMed, EMBASE databases etc.to obtain relevant research published through June 2020. Studies were considered eligible if odds ratios (ORs) and 95% confidence intervals (95% CI) were provided or calculated from the given data. The size of the combined effect was calculated using STATA 15.0 Results Our study revealed significant association between CP and IL-18 137 G > C (P = .045, OR = 1.67), 607 C > A (P = .045, OR = 1.67). The overall meta-analysis revealed significant associations between IL-18 137 G > C polymorphism and CP risk in Allele, dominant, co-dominant and recessive genetic models. The subgroup analysis also showed a significant association between the IL-18 137 G > C and risk for periodontitis and aggressive periodontitis in the Asian (GC+ CC VS. GG: P = .047, OR = 1.64,95%CI = 1.01-2.68) Conclusions IL-18 137 G > C, 607 C > A could be associated with susceptibility to periodontitis in Uyghur population. Further case-control of candidate genes studies targeting larger sample sizes and different ethnic groups are needed to arrive more accurate conclusions.
      原文链接:
    • NSTL
    • Taylor & Francis

    A Differential Immune Modulating Role of Vitamin D in Urinary Tract Infection.

    Pirdel, LeilaPirdel, Manijeh
    15页
    查看更多>>摘要：Vitamin D is known as an important modulator of numerous immune functions. We aimed to investigate the association of 25-hydroxyvitamin D [25(OH)D] with several humoral mediators of the immune system in the patients with urinary tract infection (UTI) caused by uropathogenic E. coli (UPEC). Serum levels of 25(OH)D, cytokines (interferon (IFN)-gamma, interleukin (IL)-4, IL-6, IL-10, IL-17A, tumor necrosis factor transforming growth factor (TNF)-alpha, and tumor growth factor (TGF)-beta), immunoglobulin (Ig) isotypes (IgG, IgM, and IgM), complement proteins (C3 and C4) with hemolytic activities (CH50 and AP50), and nitric oxide (NO) were evaluated in 65 patients, compared to 45 age- and sex-matched healthy controls. An insignificant decrease in 25(OH)D levels was observed in patients, compared to controls. In the patient group, elevated levels of IFN-gamma, IL-17A, and IL-10 had a significant association with the serum levels of 25(OH)D, while the levels of TGF-beta, IL-6, and TNF-alpha showed an insignificant association. The levels of IgG, C3, and NO also displayed such a statistically significant association with serum 25(OH)D levels. The AP50 levels which had significant difference were found to be not associated with serum 25(OH)D levels. Vitamin D might mediate a link between the innate and adaptive immune responses via the induction of Th1/Th17 polarization of cytokine responses and isotype regulation of antibody production, along with the maintenance of the capacity of the alternative complement pathway, in response to a UPEC infection. However, further studies are needed to validate the defined nature of the host immune response.
      原文链接:
    • NSTL
    • Taylor & Francis

    Association of TNF-alpha G-308 a Promoter Polymorphism with the Course and Outcome of COVID-19 Patients

    Saleh, AhmedSultan, AhmedElashry, Mohamed A.Farag, Ahmed...
    12页
    查看更多>>摘要：Background: Tumor necrosis factor-alpha (TNF-alpha) is one of the most important cytokines that manage the host defense mechanism, which may play a role in the pathogenesis of COVID-19 patients. The work aims to study the association of TNF-alpha G-308 A gene polymorphism with the course and outcome of COVID-19 patients in Mansoura University Hospital. Methods: 900 patients with COVID-19 infection and 184 controls were tested for TNF-alpha G-308 A promoter polymorphism. Different genotypes of TNF-alpha G-308 A were compared as regards the severity and prognosis of the disease. Results: No statistically significant difference was found between patients and controls as regards the demographic data. The AA genotype of TNF-alpha showed a higher incidence of the disease in comparison to the other genotypes. As regards the demographic and laboratory characters, no statistically significant difference was found between the different genotypes except for age, lymphopenia, CRP, and serum ferritin levels. In 336(80.0%) cases of the AA genotype, the disease was severe in comparison to 90(41.7%) cases in the GA genotype and no cases in the GG genotype with P = .001. Conclusion: People who carry the A allele of TNF-alpha polymorphism are more prone to COVID-19 infection. The AA genotype of TNF-alpha is associated with a more aggressive pattern of the disease. In those patients, the use of anti - TNF therapy may be promising.
      原文链接:
    • NSTL
    • Taylor & Francis

    Adenosine Deaminase Type II Deficiency: Severe Chronic Neutropenia, Lymphoid Infiltration in Bone Marrow, and Inflammatory Features

    Suleyman, MerveTan, CagmanUner, AysegulInkaya, Cagkan...
    9页
    查看更多>>摘要：Deficiency of adenosine deaminase type 2 (DADA2) is an autoinflammatory disease characterized with immunologic, hematologic, and neurological features. Here, we presented two patients with severe persistent chronic neutropenia, which required differential diagnosis of congenital and autoimmune neutropenia, myelodysplastic syndrome (MDS), and primary immunodeficiency diseases, including autoimmune lymphoproliferative disease. The therapy of the disease except hematopoietic stem cell transplantation is a challenging experience.
      原文链接:
    • NSTL
    • Taylor & Francis

    Investigation of Serum Total IgE and Eosinophil Levels in Different Allergic Diseases Together with the Study of Their Correlations with Various Possible Allergens in Mosul City

    Altaii, Hiyam A.Al-Tae, Firas M. D.
    21页
    查看更多>>摘要：Serum total IgE (tIgE) is frequently used in the diagnosis of allergic diseases in Mosul city and Iraq. However, neither normal nor elevated levels can exclude or confirm the diagnosis of these diseases. Here, we tried to evaluate the validity of tIgE in the diagnosis of allergic asthma(AS), allergic rhinitis(AR) and atopic dermatitis(AD) in a sample of Mosul population, to set up an optimum cut-off value for diagnosis of these diseases and to study its correlation with different parameters that might affect its level. 38 patients with AS, 27 with AR, 46 with AD and 45 healthy controls were included in this study. tIgE were determined by ELISA and compared between allergic diseases and controls. Blood eosinophilia was ascertained and correlated with tIgE levels. The geometric means of tIgE were 316.87 IU/ml (95% CI: 234.69 to 427.82) in AS, 262.07 IU/ml (95% CI:174.24 to 394.18) in AR and 270.48 IU/ml (95% CI:202.57 to 361.16) in AD compared to 16.90 IU/ml (95% CI:12.32 to 23.18) in healthy controls. tIgE in allergic diseases was significantly increased in comparison to healthy controls (P <.0001). Female gender influenced tIgE in AS, but not in AR or AD. tIgE predominated in younger age groups; however, no significant difference was found between younger and older groups. Optimum values for tIgE with best discriminative accuracy were 77 IU/ml for AS and 81 IU/ml for AR and AD. Eosinophils count appeared to be a useful adjunct, and correlate well with tIgE in the diagnosis of allergic diseases.
      原文链接:
    • NSTL
    • Taylor & Francis

    Development of a Novel Multiplex Bead-based Assay for Measuring Autoantibodies on Flow Cytometric Platform

    Chauhan, RajniGupta, NikitaTiwari, Aseem KumarRaina, Vimarsh...
    14页
    查看更多>>摘要：Background: Autoantibodies (AAbs) are important biomarkers for the diagnosis of Autoimmune Diseases (ADs). The detection of AAbs performed by current methods (indirect immunofluorescence test (IIFT)/Immunoblot (dot/line)/enzyme-linked immunosorbent assay ELISA) which have limitations in terms of performing multiple assays to arrive at laboratory diagnosis. We validated a novel multiplex bead-based assay (NMBA) that could quantify five common antibodies, simultaneously, on a flow-cytometry platform. Methods: A total of five recombinant antigens (SS-A Ro60, CENP B, RNP 70, Scl 70 and Histones) were covalently coupled onto beads and tested using known positive sera (positive for AAbs) and analyzed using flow cytometer. Results: The sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were obtained for each antigen, analyzed by both assays (NMBA and IIFT). It showed comparable or higher values for the NMBA. The Spearman's rank correlation coefficient (Rho) were >= 0.97, (P < .05), indicating that multiplexing of the five autoantigens did not alter the results obtained when antigens were tested individually. The mean intra-assay precision measured by coefficient of variation (CV) was7.56 +/- 1.6% and the mean inter-assay CV was 10.03 +/- 1.34%. The time taken from sample receipt to reporting of results was 90 minutes in NMBA as compared to 150 minutes of IIFT Conclusion: The NMBA could quantitatively measure antibodies against five autoantigens, simultaneously in patient's sera. The assay is faster, objective, reproducible, requires low sample volume, and stable. Moreover, the flow cytometer in diagnostic laboratory settings for hematological and transplant immunology tests, can also be used for testing AAbs.
      原文链接:
    • NSTL
    • Taylor & Francis

    Nephroprotection through Modifying the Apoptotic TNF-alpha/ERK1/2/Bax Signaling Pathway and Oxidative Stress by Long-term Sodium Hydrosulfide Administration in Ovalbumin-induced Chronic Asthma

    Kianian, FarzanehSeifi, BehjatKadkhodaee, MehriSadeghipour, Hamid Reza...
    17页
    查看更多>>摘要：Asthma is one of the most common respiratory diseases in the world. Nevertheless, it is reported that inflammation induced by asthma is not only restricted to the lung and may cause damaging effects on remote organs. Therefore, this study was designed to investigate the beneficial effects of long-term sodium hydrosulfide (NaHS) administration on lung inflammation and oxidative stress markers to protect the kidney during chronic asthma. BALB/c mice were divided into three groups (n = 5-7): control, asthma and NaHS. Except the control group, sensitization and challenge were performed with ovalbumin. The NaHS group intraperitoneally received 14 mu mol/kg NaHS 30 min before each challenge. 24 h after the last challenge, samples of bronchoalveolar lavage fluid (BALF), plasma, lung and kidney tissues were collected. NaHS administration significantly decreased total white blood cell count, percentages of eosinophils, neutrophils and macrophages and increased percentage of lymphocytes. Administration of NaHS considerably decreased the levels of BALF interleukin-13, plasma tumor necrosis factor-alpha (TNF-alpha), lung malondialdehyde (MDA) and lung phosphorylated nuclear factor-kappa B (p-NF-kappa B) expression and scores of peribronchial inflammatory cell infiltration, goblet cell hyperplasia and subepithelial fibrosis and increased the activity of lung superoxide dismutase (SOD). The MDA levels and expressions of p-ERK1/2 and Bax were decreased and SOD activity and expressions of Bcl-2 and p-Akt were significantly increased in kidney tissues by NaHS administration. Administration of NaHS decreased renal oxidative stress indices and reduced apoptosis by the inhibition of TNF-alpha/ERK1/2/Bax. Therefore, H2S may have an essential role in renal protection during asthma.
      原文链接:
    • NSTL
    • Taylor & Francis