scholarly journals Interleukin-18, Functional IL-18 Receptor and IL-18 Binding Protein Expression in Active and Latent Tuberculosis

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 451
Author(s):  
Sebastian Wawrocki ◽  
Grzegorz Kielnierowski ◽  
Wieslawa Rudnicka ◽  
Michal Seweryn ◽  
Magdalena Druszczynska

A thorough understanding of the processes modulating the innate and acquired immune response to Mycobacterium tuberculosis (M.tb) infection in the context of gene expression is still a scientific and diagnostic problem. The study was aimed to assess IL-18, IL-18 binding protein (IL-18BP), IL-18R, IFN-γ, and IL-37 mRNA expression in patients with active tuberculosis (ATB) and healthy volunteers with latent M.tb-infection (LTB) or M.tb-uninfected healthy controls (Control). The relative mRNA expression was assessed in the buffy coat blood fraction using the qPCR method. In total, 97 BCG-vaccinated Polish adults were enrolled in the study. The relative expression of IL-18 and IL-18BP mRNA was significantly elevated in the ATB and LTB groups. In ATB, but not LTB individuals, the overexpression of IL-18 and IL-18BP, as well as a significant increase in IFN-γ mRNA expression, might be considered as a manifestation of active tuberculosis disease. No statistically significant differences were observed in the IL-37 mRNA expression among the studied groups. Particularly noteworthy is the outstanding reduction in the relative expression of IL-18R mRNA in the LTB group as compared to the ATB and Control group. Reduced expression of IL-18R in LTB group may, at least partially, prevent the development of a pathological inflammatory reaction and promote the maintenance of homeostatic conditions between host immunity and M.tb.

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Kexin Zhu ◽  
Dong Yu ◽  
Jiahui An ◽  
Yufeng Li

AbstractGlässer’s disease is caused by the agent Glaesserella parasuis and is difficult to prevent and control. Candidate screening for subunit vaccines contributes to the prevention of this disease. Therefore, in this study, the inactivated G. parasuis reference serovar 5 strain (G. parasuis-5) was used to generate specific monoclonal antibodies (mAbs) to screen subunit vaccine candidates. Six mAbs (1A12, 3E3, 4C6, 2D1, 3E6, and 4B2) were screened, and they all reacted with the G. parasuis serovar 5 strain according to laser confocal microscopy and flow cytometry (FCM). Indirect enzyme-linked immunosorbent assay (ELISA) showed that one mAb 2D1, can react with all 15 reference serovars of G. parasuis. Protein mass spectrometry and Western blot analysis demonstrated that mAb 2D1 specifically reacts with Fe (3+) ABC transporter substrate-binding protein. A complement killing assay found that the colony numbers of bacteria were significantly reduced in the G. parasuis-5 group incubated with mAb 2D1 (p < 0.01) in comparison with the control group. Opsonophagocytic assays demonstrated that mAb 2D1 significantly enhanced the phagocytosis of 3D4/21 cells by G. parasuis (p < 0.05). RAW264.7 cells with stronger phagocytic ability were also used for the opsonophagocytic assay, and the difference was highly significant (p < 0.01). Passive immunization of mice revealed that mAb 2D1 can eliminate the bacteria in the blood and provide protection against G. parasuis-5. Our study found one mAb that can be used to prevent and control G. parasuis infection in vivo and in vitro, which may suggest that Fe (3+) ABC transporter substrate-binding protein is an immunodominant antigen and a promising candidate for subunit vaccine development.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Youyou Wang ◽  
Huijun Ren ◽  
Zhaohu Pan ◽  
Ben Liu ◽  
Fan Lin

Objective. To investigate the expression of miR-338-3p in nasopharyngeal carcinoma (NPC) and its relationship with STAT3 mRNA expression as well as their relationship with clinical pathological parameters and prognosis of patients. Methods. From September 2016 to September 2018, 71 patients with NPC were selected as the NPC group, and 71 samples of NPC tissues were collected during the operation. A total of 23 patients who underwent biopsy due to chronic nasopharyngitis were selected as the control group and 23 nasopharyngeal mucosal tissues were collected. The expressions of miR-338-3p and STAT3 mRNA in nasopharyngeal tissue of two groups were detected by real-time quantitative PCR, and the relationship between the two was analyzed. To collect clinical data of NPC patients and analyze the relationship between the expressions of miR-338-3p and STAT3 in NPC tissues and clinical pathological parameters of the patients, we followed up the patients with nasopharyngeal carcinoma for three years to observe the relationship between miR-338-3p, STAT3, and the prognosis of the patients. Results. The relative expression levels of miR-338-3p in nasopharyngeal tissues of the NPC group and the control group were 0.39 ± 0.05 and 1.01 ± 0.09, respectively ( P  < 0.05). The relative expression levels of STAT3 mRNA in nasopharyngeal tissues of the NPC group and the control group were 3.82 ± 0.21 and 1.04 ± 0.11, respectively ( P  > 0.05). miR-338-3p was negatively correlated with the relative expression of STAT3 mRNA in nasopharyngeal carcinoma (r = 0.038, P  > 0.05). The expression of miR-338-3p was related to the age of the patient, clinical TNM stage, T stage, and distant metastasis (all P  < 0.05). STAT3 expression was correlated with clinical TNM stage, T stage, and distant metastasis in our patient ( P  < 0.05). The expressions of miR-338-3p and STAT3 in nasopharyngeal carcinoma tissues from different gender, histological type, N stage, M stage, and degree of differentiation showed no statistical differences ( P  > 0.05). The survival rate of the group with low miR-338-3p expression was significantly lower than that of the group with high miR-338-3p expression ( P  > 0.05). The survival rate of patients with the high STAT3 expression group was significantly lower than that of patients with the low STAT3 expression group ( P  > 0.05). Conclusion. There is a negative correlation between the low expression of miR-338-3p and the high expression of STAT3 in NPC, which are all related to the TNM stage, T stage, and prognosis of the patient.


2014 ◽  
Vol 34 (5) ◽  
pp. 497-505 ◽  
Author(s):  
F Guo ◽  
YB Sun ◽  
L Su ◽  
S Li ◽  
ZF Liu ◽  
...  

Paraquat (PQ) is one of the most widely used herbicides in the world and can cause pulmonary fibrosis in the cases with intoxication. Losartan, an angiotensin II type 1 receptor antagonist, has beneficial effects on the treatment of fibrosis. The aim of this study was to examine the effect of losartan on pulmonary fibrosis in PQ-intoxicated rats. Adult male Sprague Dawley rats ( n = 32, 180–220 g) were randomly assigned to four groups: (i) control group; (ii) PQ group; (iii) PQ + losartan 7d group; and (iv) PQ + losartan 14d group. Losartan treatment (intragastrically (i.g.), 10 mg/kg) was performed for 7 and 14 days after a single i.g. dose of 40 mg/kg PQ. All rats were killed on the 16th day, and hematoxylin–eosin and Masson’s trichrome staining were used to examine lung injury and fibrosis. The levels of hydroxyproline and transforming growth factor β1 (TGF-β1), matrix metallopeptidase 9 (Mmp9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) messenger RNA (mRNA) expression and relative expression levels of collagen type I and III were also detected. PQ caused a significant increase in hydroxyproline content, mRNA expression of TGF-β1, Mmp9, and TIMP-1, and relative expression levels of collagen type I and III (  p < 0.05), while losartan significantly decreased the amount of hydroxyproline and downregulated TGF-β1, Mmp9, and TIMP-1 mRNA and collagen type I and III expressions (  p < 0.05). Histological examination of PQ-treated rats showed lung injury and widespread inflammatory cell infiltration in the alveolar space and pulmonary fibrosis, while losartan could markedly reduce such damage and prevent pulmonary fibrosis. The results of this study indicated that losartan could reduce lung damage and prevent pulmonary fibrosis induced by PQ.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3847-3847 ◽  
Author(s):  
Yunfeng Cheng ◽  
Shanhua Zou ◽  
Feng Li

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against self-antigens and T-cell mediated cytotoxicity. Toll-like receptors (TLRs) are pattern recognition receptors important in mediating the immune response and their activation can lead to production of cytokines. Recent data suggest that TLR2 and TLR4 are crucial for the production of inflammatory cytokines and play central role in autoimmune diseases, yet little is known about their roles in ITP. Here we examined the gene expressions of TLR2 and TLR4 in ITP patients. We hypothesize that significant differences will exist between pre-treatment and post-treatment in ITP patients with similar changes reflected in the plasma concentration of cytokines. Total RNA was extracted from mononuclear cells obtained from 12 ITP patients and 15 healthy subjects. TLR2 and TLR4 mRNA expression levels were analyzed using a quantitative real-time PCR method and their protein expressions were validated by western blot. Plasma concentrations of cytokines IL-2, IFN-γ and TNF-α were measured by ELISA. Correlation analyses were carried out between the mRNA expression levels of TLR2 or TLR4 and the plasma levels of IL-2, IFN-γ and TNF-α. The gene expression of TLR2 and TLR4 were significantly increased in ITP patients comparing to healthy control group (p < 0.05 and p < 0.01, respectively). In addition their mRNA expression levels were decreased back into normal range after remission in 8 patients (p > 0.05, compared to healthy control group). Significantly positive correlations were found between the TLR2 mRNA expression level and the plasma concentration of IFN-γ or TNF-α (R = 0.75, p < 0.05; R = 0.83, p < 0.05, respectively). Changes in the gene expression of TLR4 and in the plasma concentration of IFN-γ or TNF-α were also significantly correlated (R = 0.82, p < 0.05; R = 0.88, p < 0.05, respectively). Directional changes in TLR2 / TLR4 and IFN-γ /TNF-α expression were concordant. However, there was no correlation found between TLR2 / TLR4 and IL-2. Differences in TLR2 and TLR4 expression strongly correlated with changes in IFN-γ and TNF-α suggest that the increased gene expressions of TLR2 and TLR4 in ITP patients may contribute to the pathophysiological progression of this disease by increasing the secretion of IFN-γ and TNF-α. Additional studies need to be performed to further clarify the role of TLRs -cytokines pathway in ITP.


2000 ◽  
Vol 99 (4) ◽  
pp. 343-348 ◽  
Author(s):  
Kohichi TAMURA ◽  
Shinzo TAKAMORI ◽  
Hiroharu MIFUNE ◽  
Akihiro HAYASHI ◽  
Kazuo SHIROUZU

Atrial natriuretic peptide (ANP) is a cardiac hormone which affects endothelial cell function through a receptor-mediated process. Pneumonectomy is a common thoracic surgical procedure that can cause pulmonary oedema in the remaining lung. Few reports have investigated the aetiology of this complication. The aim of this study was to determine the changes in ANP concentration and expression of its receptors following pneumonectomy as a possible aetiology for postpneumonectomy pulmonary oedema (PPE). We compared plasma ANP concentrations, cGMP concentrations, and natriuretic peptide receptor (NPR)-A mRNA and NPR-C mRNA expression in rat lung 3 h after pneumonectomy (n = 5) or a sham operation (n = 5). The ANP concentrations in plasma and lung tissue in the pneumonectomy group were significantly higher than in the control group (749.5 versus 202.7 pgċml-1, P < 0.01; 33.1 versus 6.8 ngċg-1 wet tissue, P < 0.01 respectively). The level of ANP mRNA expression in the pneumonectomy group was significantly higher than in the control group (1.44 versus 0.41 relative ANP mRNA expression, P < 0.05). The concentration of cGMP and the level of NPR-A mRNA expression were not significantly different between the pneumonectomy and control groups. The level of NPR-C mRNA expression in the pneumonectomy group was significantly higher than in the control group (4.17 versus 2.19 relative NPR-C mRNA expression, P < 0.01). These findings suggest that changes in pulmonary ANP and NPR-C expression may contribute to the development of PPE in the remaining lung in the acute phase following pneumonectomy.


2013 ◽  
Vol 111 (4) ◽  
pp. 625-632 ◽  
Author(s):  
Takayuki Kubota ◽  
Naoki Shimojo ◽  
Ken Nonaka ◽  
Masakatsu Yamashita ◽  
Osamu Ohara ◽  
...  

The consumption of probiotics by pregnant and lactating women may prevent the onset of allergic disorders in their children by increasing the concentrations of immunoactive agents such as cytokines in breast milk. Prebiotics such as fructo-oligosaccharides (FOS) increase the number of beneficial organisms such as bifidobacteria. Thus, prebiotics may have an effect similar to that of probiotics. The objective of the present study was to carry out a comprehensive analysis of mRNA expression in human milk cells to identify changes in the concentrations of cytokines in breast milk after the consumption of FOS (4 g × 2 times/d) by pregnant and lactating women. The microarray analysis of human milk cells demonstrated that the expression levels of five genes in colostrum samples and fourteen genes in 1-month breast milk samples differed more than 3-fold between the FOS and control groups (sucrose group). The mRNA expression level of IL-27, a cytokine associated with immunoregulatory function, was significantly higher in 1-month breast milk samples obtained from the FOS group than in those obtained from the control group. In addition, the protein concentrations of IL-27 in colostrum and 1-month breast milk samples were significantly higher in the FOS group than in the control group. In conclusion, the consumption of FOS by pregnant and lactating women increases the production of IL-27 in breast milk. Future studies will address the association of this phenomenon with the onset of allergic disorders in children.


2021 ◽  
Vol 12 (1) ◽  
pp. 215
Author(s):  
Hae Sung Lee ◽  
Hyun Ju Oh ◽  
Kihae Ra ◽  
Jong-Hee Kim

This study aimed to investigate the effect of a treadmill exercise on hematological and serum biochemical parameters and the expression of immune-related cytokine genes in leukocytes. For the experiment, six healthy adult dogs were divided into exercise and control groups. The exercise group performed an endurance exercise three times a week for four weeks. Blood samples were collected before exercise, two weeks after exercise, and post-exercise, and hematological and serum biochemical analysis and cytokine gene analysis were conducted. In the exercise group, white blood cell count (WBC), aspartate aminotransferase, serum alkaline phosphatase, and glucose levels were significantly decreased, but there was no change in the control group. The mRNA expression of TNF-α, IFN-γ, IL-1β, and IL-4 was significantly decreased in the exercise group compared to the control group. There was no difference in IL-6, IL-8, and IL-10 mRNA expression between groups. The results in the current study demonstrate that short-term moderate-intensity endurance exercise alters WBC levels and mRNA cytokine expression in leukocytes and may have a meaningful effect on immune health in dogs.


2021 ◽  
Vol 18 (5) ◽  
pp. 1141-1147
Author(s):  
Fang Yu ◽  
Shen Cailiang

Purpose: To investigate the effect of combination of vitamin D and anti-tuberculosis drugs on serum interleukin-1β (IL-1β), interferon-γ (IFN-γ) and helper T 17 (Th17) cell-associated cytokine levels for the treatment of spinal tuberculosis (TB). Methods: Ninety-two spinal TB patients were assigned without bias to two groups (46/group): study group (vitamin D combined with anti-TB drug group) and control group (anti-TB drug group). After treatment for 8 weeks, clinical effectiveness, adverse reactions, visual analog scale (VAS) score, spinal cord injury grade, and serum levels of IL-1β, IFN-γ, Th17, IL-10, TGF-β1, IL-17 and IL-23 were assayed with ELISA, and compared between groups. Results: Study group total effectiveness was significantly higher than that in the control group (95.65 % vs 80.43 %, p < 0.05). Before drug administration, VAS score, degree of spinal cord injury and serum levels of IL-1β, IFN-γ, IL-10, TGF-β1, IL-17 and IL-23 were comparable in the study and control patients (p > 0.05). However, post-treatment, these parameters significantly decreased in both groups (p < 0.05), but were markedly lower in study group patients, relative to controls (p < 0.05). Conclusion: The use of combined treatment of vitamin D and anti-TB drugs is an effective and safe way to alleviate inflammatory response and improve the immunity of spinal TB patients via the regulation of the levels of Th17 cell-related factors.


Author(s):  
Salim Can ◽  
Ayse Sahin ◽  
Nazan Dalgic ◽  
Deniz Aygün

Abstract Objective This study aimed to investigate interferon-gamma-inducible protein-10 (IP-10) values in serum and urine in pediatric patients in the diagnosis of active tuberculosis (TB) or latent TB infection (LTBI). It also aimed to investigate whether it can be used as a biomarker to distinguish between active TB and LTBI. Methods Our study comprised active TB (25 patients), LTBI (25 patients), and the “infected” group (50 patients) formed by combining the two groups. As the control group, 37 healthy children were included in the study. TB skin test, plasma IP-10, and urine IP-10 measurements were performed in all patients included in the study. An additional QuantiFERON-TB Gold In-Tube (QFT-GIT) test was performed on patients evaluated as active TB or LTBI. Results Plasma IP-10 levels of the patients in the active TB, LTBI, and the “infected” groups were significantly higher than the control group (p = 0.022, p = 0.028, and p = 0.007, respectively). Urine IP-10 was successful in distinguishing the active TB and “infected” groups from the control group (p = 0.007 and p = 0.047, respectively). Also, in the combined use of the tests, when QFT-GIT and urine IP-10 were positive together, active TB and LTBI could be distinguished (p = 0.044). Urine IP-10 levels were found to be significantly higher in those with pulmonary TB than those with extrapulmonary TB (p = 0.012). Conclusion Our findings suggest that IP-10 can be used as a useful biomarker in the diagnosis of active TB in children.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5084-5084 ◽  
Author(s):  
Ni Zhu ◽  
Huafang Wang ◽  
Haowen Xiao ◽  
Ruxiu Tie ◽  
He Huang

Abstract PTPN21 Plays a Role in Occurrence and Relapse of Acute Lymphoblastic Leukemia by Promoting the Proliferation of Acute Lymphoblastic Leukemic Cells via Activating MAPK Signal Pathways Accumulating evidences have uncovered the relevance of overexpression in protein tyrosine phosphatases (PTPs) to hematologic malignancies. We analyzed 21 acute lymphoblastic leukemia (ALL) patients and 17 nonmalignant patients as control group in a pilot study. Mononuclear cells were separated from bone marrow samples of these patients via bone marrow aspiration. By real-time fluorescence quantitative PCR, we analyzed the mRNA expression of PTPN21 (tyrosine-protein phosphatase non-receptor type 21), a member of protein tyrosine phosphatases. The mRNA expression of PTPN21 in ALL group was higher than that in control group (10.86¡À2.266 vs. 6.112¡À0.8385, P£¾0.05, Figure 1A), although without significant differences. We divided 21 ALL patients into two groups: new diagnosis or relapse (61.9%, group A) and remission after chemotherapy or HSCT (38.1%, group B). The mRNA expression of PTPN21 in group A was significantly higher than that in control group (15.17¡À3.091 vs. 6.112¡À0.8385, P£¼0.01, Figure 1B) and also higher than that in group B (15.17¡À3.091 vs. 3.845¡À0.731, P£¼0.05, Figure 1B). There was no significant difference between group B and control group (3.845¡À0.731 vs. 6.112¡À0.8385, P£¾0.05, Figure 1B). These data implied that the overexpression of PTPN21 may relate to the occurrence and relapse of ALL. In order to define the specific mechanisms, we overexpressed PTPN21 in three ALL cell lines by lentiviral transfection, including Jurkat, NALM-6 and Reh cells. We assessed cell cycles by flow cytometry after cells were serum-deprived overnight and stimulated with EGF (epidermal growth factor) for 30 min. We found that cells in G0 phase dramatically decreased and cells in S/G2/M phases dramatically increased after overexpression of PTPN21 (Figure 2). We also detected apoptosis by flow cytometry and found no significant differences between overexpression group and control group. These data demonstrated that overexpression of PTPN21 promoted the proliferation of ALL cells, however didn`t affect the apoptosis of ALL cells. Next we attempted to figure out the mechanisms that PTPN21 promoted proliferation of ALL cells. We discovered the promotion of dephosphorylation of SRC residue Y527 by western blot analysis, which could stimulate SRC activity. The direct combination of PTPN21 and SRC was demonstrated by immunoprecipitation. The downstream MAPK pathways were also activated by phosphorylation. To be specific, JNK and ERK pathways were activated in Jurkat cells while P38 and ERK pathways were activated in NALM-6 cells. In addition, JNK, P38 and ERK pathways were all activated in Reh cells. In conclusion, our study revealed that PTPN21 may play a role in the occurrence and relapse of ALL by promoting the proliferation of ALL cells via activating SRC and downstream MAPK signal pathways. Disclosures No relevant conflicts of interest to declare.


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