T Lymphocytes and Th1/Th2 Cytokines in Peripheral Blood of Patients with Recurrent Genital Herpes

Objective: This study analyzed the T lymphocytes and Th1/Th2 type cytokine profile shift in the peripheral blood ofpatients with recurrent genital herpes (RGH). Methods: Immunofluorescent staining or cell surface antigenand intracellular cytokines(IL-2、IL-4、IL-12、IFN-r)inperipheral blood from 20 RGH patients and 10 controls wereanalyzed using flow cytometric techniques. Results: RGH patients had signiflcantly lower levels ofCD3^+T cells, CD4^+T cells and CD4^+ T/ CD8^+ T cells ratiocompared to control levels (P<0.001), and IL-2-producing,IFN-r-producing and IL-12-producing T cells were increasedin RGH patients (CD4^+T: P<0.001, CD8^+T: P<0.05respectively), whereas IL-4-producing T cells were increased inRGH patients compared to controls (CD4^+T: P<0.05; CD8^+T:P<0.001 respectively). Conclusions: RGH patients have T lymphocyte subsetvariations and Th1/Th2 cytokine changes. The increase in Th2cells Th1/Th2 imbalance may have important implications forRGH pathogenesis.

Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells

· AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptides1169 to 1191 of the interphotoreceptor binding protein(IRBP). Rapamycin(0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4 +CD25 + regulatory T cells(Tregs)from rat spleen were detected by flow cytometry.·RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro.Rapamycin also significantly increased TGF-β1production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore,rapamycin decreased the ratio of Th17 cells/CD4 +T cells and upregulated Tregs in EAU, as detected by flow cytometry.·CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU.Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.

Effects of the Overall Alkaloid of a Traditional Chinese Medicine “Tongbiling” on the Cytokine Expression in Th1 and Th2 Cells of Rheumatoid Arthritis and Their Signaling Pathway

To investigate the effects of overall alkali of a traditional Chinese medicine “Tongbiling” (brucine and strychnine alkaloids in main) on the cytokines expression in Th1 and Th2 cells in the synovial fluid of patients with rheumatism arthritis and their signal pathway, the mononuclear cells in the synovial fluid (SFMC) of patients were isolated by Ficoll-Hypaque gradient centrifugation, and the CD3 + CD69 + and CD3 + HLA-DR antigen were analyzed by flow cytometry in comparison with those of the peripheral blood. The rest of cells were cultured after resuspension with RPMI 1640 culture medium. Phorbol 12,13-dibutyrate (PDB) and ionomycin were added successively into the culture with various concentration of overall alkali Tongbiling (TBL). After 4 h of cultivation, the expression of IFN-γ and IL-4 in CD3 + cells were analyzed by flow cytometry. The influence of overall alkali TBL (100?mg/L) on the intracellular calcium was investigated after Fluo-3/AM labeling and stimulation with PDB and ionomycin at 1, 2, 4 and 10?min, and the influence of TBL on the expression of CD3 + CD69 + cells were determined with stimulation of PDB for 24?h in the whole blood lymphocytes culture. It was found that the percentage of T cells bearing CD69 was significantly up-regulated (77%), while that of T cells bearing HLA-DR was 44% in the synovial mononucleated cells. After PDB and ionomycin stimulation, the expression of IFN-γ in CD3 + cells were up-regulated, but there was no change on the expression of IL-4 in CD3 + cells, indicating that ratio of Th1/Th2 was significantly increased and Th cells differentiate to Th1 cells in mainly. Four concentrations of overall alkaloid of TBL (200?mg/L, 100?mg/L, 50?mg/L, 25?mg/L) could down-regulated the expression of IFN-γ in CD3 + cells and the Th1/Th2 ratio obviously, but all the concentrations of the overall alkaloids had no effect on the expression of IL-4 in CD3 + cells. 100?mg/L concentration of the overall alkaloid did not down-regulate the intracellular calcium level. Each concentration of the overall alkaloid could down-regulated the expression CD69 obviously on the PDB-activated mouse T cells. It concluded from the above observations that the overall alkaloid of TBL could relieve the inflammatory and immune damages by suppressing the expression of Th1 type cytokines and Th1 cell differentiation, regulating the imbalance of Th1/Th2 cells and inhibiting the early activation of the T lymphocytes bearing CD69. There was no remarkable influence on the intracellular calcium signaling transduction pathway. The inhibitory effected on T cells to express IFN-γ might be due to the suppression of PKC-MAPK signaling pathway. From the standpoint of traditional Chinese medicine, this might be due to the regulation of “Yin” and “Yang” imbalance of joints to modify the pathological status in rheumatoid arthritis. This study provided an experimental basis for the application of overall alkaloids of TBL in the treatment of rheumatoid arthritis.

Regulatory T cells percentage in peripheral blood before and after eradication of <i>Helicobacter pylori</i>

Helicobacter pylori (H. pylori) induces gastroduodenal diseases and vigorous humural and cellular immune abnormalities. In order to clarify the immunological changes before and after eradication of H. pylori, the percentages and ratios of the following cells in the peripheral blood of 32 H. pylori-infected patients and 25 control subjects were analyzed: CD4+ T cells, CD8+ T cells, T helper 1 cells (Th1), T helper 2 cells (Th2), CD4+CD25+ T cells, Foxp3+ regulatory T cells (Treg), CD4/CD8 ratio, and Th1/Th2 ratio. CD4/CD8 ratio was significantly higher in H. pylori-infected patients before (mean ± SD, 2.9 ± 1.9) and after (mean ± SD, 2.8 ± 1.6) eradication of H. pylori than in control subjects (mean ± SD, 2.1 ± 0.9). The percentage of Th2 cells was significantly higher in H. pylori-infected patients (mean ± SD, 2.6 ± 1.1) than in control subjects (mean ± SD, 1.9 ± 1.1;p < 0.02). The percentage of Th2 cells after eradication of H. pylori (mean ± SD, 2.3 ± 1.4) was lower than that before eradication. There was no significant difference between control subjects (mean ± SD, 4.1% ± 1.5%) and patients before H. pylori eradication (mean ± SD, 4.5% ± 2.4%) in the percentage of Tregs, but the percentage was significantly higher in patients after H. pylori eradication (mean ± SD, 5.2% ±2.6%) than in control subjects. The function of peripheral induced Tregs was reported to suppress the excessive immune reaction in chronic inflammation. These data suggest that Tregs may proliferate and be activated to suppress the activation of humoral immunity in H. pylori-infected patients, and these changes continue after 3 months or later of successful eradication of H. pylori.

Phosphorylation of Protein Kinase Akt by Mtorc2 in Peripheral Blood Mononuclear Cells of Patients with Cancer and Diabetes

Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes.Macrophages and lymphocytes are involved in the pathogenesis of diabetes,diabetic atherosclerosis,formation of insulin resistance as well as immune response to cancer and tumor maintenance.The aim of the study was to determine the Akt activation by mTORC2 in peripheral blood mononuclear cell(PBMC)of patients with type 2 diabetes and cancer.The following groups were studied:control group,patients with type 2 diabetes,cancer patients and patients with both cancer and diabetes.The amounts of phospho-Akt(р-S473)and phospho-p70S6K1(p-T389)were determined using ELISA kits.The amount of phosphorylated Akt significantly increases in PBMC of patients with cancer.There was no effect in PBMC from patients with type 2 diabetes and significant decrease in the amount of phospho-Akt in PBMC of the patients group both with cancer and diabetes.p70S6K1 activation was observed in PBMC of the groups 2 and 3 patients.Thus,chronic diseases such as type 2 diabetes and cancer can affect the signaling mechanisms in blood cells.The state of Akt phosphorylation in leukocytes can indicate the activity of mTORC1 and its substrates,which may be important for the evaluation of the pathological process and the efficacy of the drugs.

GATA-3 promotes Th2 responses through three different mechanisms： induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Thl cell-specific factors

Naive CD4 T cells can differentiate into at least two different types ofT helpers, Thl and Th2 cells. Th2 cells, capable of producing IL-4, IL-5 and IL-13, are involved in humoral immunity against extracellular pathogens and in the induction of asthma and other allergic diseases. In this review, we summarize recent reports regarding the transcription factors involved in Th2 differentiation and cell expansion, including StatS, Gfi- 1 and GATA-3. Stats activation is necessary and sufficient for IL-2-mediated function in Th2 differentiation. Enhanced Stats signaling induces Th2 differentiation independent of IL-4 signaling; although it does not up-regulate GATA-3 expression, it does require the presence of GATA-3 for its action. Gfi-1, induced by IL-4, promotes the expansion of GATA-3-expressing cells. Analysis of conditional Gata3 knockout mice confirmed the critical role of GATA-3 in Th2 cell differentiation （both IL-4 dependent and IL-4 independent） and in Th2 cell proliferation and also showed the importance of basal GATA-3 expression in inhibiting Thl differentiation.

All-transRetinoic Acid Regulates Th1/Th2 Balance in CD4+T cells When GATA-3 is Deficient

The essential effect of vitamin A on immune function occurs through various mechanisms including direct effect on ThloTh2 balance modulation. However, it is unclear whether or not vitamin A can regulate Thl-Th2 balance under a strong Thl-polarizing condition. Therefore, the purpose of our study was to examine the effect of vitamin A metabolite allotrans retinoic acid （ATRA） on ThloTh2 differentiation in CD4~ T cells under GATA-3 deficiency, which can induce Thl-polarizing condition. In the present study, GATA-3 deficiency T cells were induced by siRNA and checked by real-time quantitative PCR and western blot. GATA-3 deficiency CD4＋ T cells and normal CD4＋ T were treated for 48 h with or without ATRA.

Activated rat hepatic stellate cells influence Th1/Th2 profile in vitro

AIM: To investigate the effects of activated rat hepatic stellate cells(HSCs) on rat Th1/Th2 profile in vitro.METHODS: Growth and survival of activated HSCs and CD4+ T lymphocytes cultured alone or together was assessed after 24 or 48 h. CD4+ T lymphocytes were then cultured with or without activated HSCs for 24 or 48 h and the proportion of Th1 [interferon(IFN)-γ+] and Th2 [interleukin(IL)-4+] cells was assessed by flow cytometry. Th1 and Th2 cell apoptosis was assessed after 24 h of co-culture using a caspase-3 staining procedure. Differentiation rates of Th1 and Th2 cells from CD4+ T lymphocytes that were positive for CD25 but did not express IFN-γ or IL-4 were also assessed after 48 h of co-culture with activated HSCs. Galectin-9 expression in HSCs was determined by immunofluorescence and Western blotting. ELISA was performed to assess galectin-9 secretion from activated HSCs.RESULTS: Co-culture of CD4+ T lymphocytes with activated rat HSCs for 48 h significantly reduced the proportion of Th1 cells compared to culture-alone conditions(-1.73% ± 0.71%; P < 0.05), whereas the proportion of Th2 cells was not altered; the Th1/Th2 ratio was significantly decreased(-0.44 ± 0.13; P < 0.05). In addition, the level of IFN-γ in Th1 cells wasdecreased(-65.71 ± 9.67; P < 0.01), whereas the level of IL-4 in Th2 cells was increased(82.79 ± 25.12; P < 0.05) by co-culturing, as measured by mean fluorescence intensity by flow cytometry. Apoptosis rates in Th1(12.27% ± 0.99%; P < 0.01) and Th2(1.71% ± 0.185%; P < 0.01) cells were increased 24 h after co-culturing with activated HSCs; the Th1 cell apoptosis rate was significantly higher than in Th2 cells(P < 0.01). Galectin-9 protein expression was significantly decreased in HSCs only 24 h after coculturing(P < 0.05) but not after 48 h. Co-culture for 48 h significantly increased the differentiation of Th1 and Th2 cells; however, the increase in the proportion of Th2 cells was significantly higher than that of Th1 cells(1.85% ± 0.48%; P < 0.05).CONCLUSION: Activated rat HSCs lower the Th1/Th2 profile, inhibiting the Th1 response and enhancing the Th2 response, and this may be a novel pathway for liver fibrogenesis.

Correlation between circulating myeloid-derived suppressor cells and Th17 cells in esophageal cancer

AIM: To perform a comprehensive investigation into the potential correlation between circulating myeloidderived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA). METHODS: A total of 31 patients newly diagnosed with ECA and 26 healthy subjects were included in the current study. The frequencies of MDSCs and Th17 cells in peripheral blood were determined by flow cytometry. The mRNA expression of cytokines, arginase 1 (Arg1) and inducible NO synthase (iNOS) in peripheral blood mononuclear cells (PBMCs) and plasma Arg1 were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: There was an increased prevalence of MDSCs in the peripheral blood from ECA patients (15.21% ± 2.25%) when compared with healthy control (HC) (1.10% ± 0.12%, P < 0.0001). The plasma levels of Arg1 in ECA patients were significantly higher than those in HC (28.28 ± 4.10 ng/mL vs 9.57 ± 1.51 ng/ mL, P=0.0003). iNOS mRNA levels in the peripheral blood of ECA patients also showed a threefold increase compared with HC (P=0.0162). The frequencies of Th17 cells (CD4 + IL-17A + ) were significantly elevated in ECA patients versus HC (3.50% ± 0.33% vs 1.82% ± 0.19%, P=0.0001). Increased mRNA expression of IL-17 and ROR-γt was also observed in ECA patients compared with HC (P=0.0041 and P=0.0004, respectively), while the mRNA expression of IL-6 and tumor necrosis factor-α (TNF-α) showed significant decreases (P=0.0049 and P < 0.0001, respectively). No obvious correlations were found between the frequencies of MDSCs and Th17 cells in the peripheral blood from ECA patients(r=-0.1725, P=0.3534). Arg1 mRNA levels were positively correlated with levels of IL-6 (r=0.6404, P=0.0031) and TNF-α (r=0.7646, P=0.0001). Similarly, iNOS mRNA levels were also positively correlated with levels of IL-6 (r=0.6782, P=0.0007) and TNF-α (r=0.7633, P < 0.0001). CONCLUSION: This study reveals the relationship between circulating MDSCs and Th17 cells, which may lead to new immunotherapy approaches for ECA based on the associated metabolites and cytokines.

Influence of the invasion of peripheral blood mononuclear cells by hepatitis B virus on immune response of the patients with chronic hepatitis B

Objective:To exploretheinfluenceof HBVinvasionintoperipheralbloodmononuclearcells(PBMC)on theimmuneresponseof patientswithchronichepatitisB.Method s:Thecytokinelevelsintheculturesupernatantof PBMCfrom56patientswithchronichepatitisB weredeterminedby ELISA,andPCRwasemployedto amplifythe HBVDNA.Results:Thelevelsof IFN-γinpatientswithhepatitisB waslowerthanthosetof thecontrol,butthe differencewasnotstatisticallysignificant,whilethelevelsof IL-4weresignificantlyhigherthanthoseof thecontrol(P<0.01).Theserumlevelsof HBVDNAwerenegativelycorrelatedwiththatof IFN-γin culturesupernatantsof PBMC.Thirty-fivepatientspositiveof HBVDNA inthePBMCswereidentifiedfrom56patientswithhepatitisB,andtheirIFN-γlevelprovedto be significantlydifferent.Conclusions:Th2cell-mediatedimmuneresponseis predo-minantin chronichepatitisB whichis associatedwiththechronicityof HBVinfection.HBVinvasionintothe PBMCsmayaffectTh1andTh2cell-mediatedimmuneresponseof thepatientswithchronichepatitisB.

Impact of Bisphenol A (BPA) and Free Fatty Acids (FFA) on Th2 Cytokine Secretion from INS-1 Cells

Bisphenol A (BPA) is used in huge amounts for many plastic products and is a hormone (estrogen) disrupting agent. BPA as well as FFAs may be deleterious for the immune system. The aim was to identify Th2 cytokines and some of their signal transduction mechanisms in INS-1 cells, an insulin secreting cell line. Screening using a proteome profile indicated an increase of IL-1, IL-2, IL-4, IL-6, IL-10, IL-13 and IL-17 by BPA. Also FFAs (in combination with LPS) were positive. In detailed quantitative measurements, these results were confirmedly indicating a complex array of pro-and anti-inflammatory potential. The interaction of BPA with 17β-estradiol was non-additive with respect to IL-4 and IL-6 release and additive with respect to FFA interaction indicating same and different mechanisms of action, respecttively. As signal transduction PI3K (Wortmannin-sensitive) and STAT-3/6 (Tofacitinib-sensitive) are involved in various effects, INS-1 cells release several cytokines due to BPA and FFA attack which may be involved in disturbance of glucose homoeostasis and type 1 diabetes.

斑秃患者外周血单个核细胞产生Th1/Th2细胞因子研究

目的:研究斑秃患者外周血单个核细胞产生Th1型细胞因子(如IFN-γ)和Th2型细胞因子(如IL-4、IL-10)水平,探讨其在斑秃发病中所起的作用及与病情活动性的关系。方法:采用ELISA双抗体夹心法检测36例斑秃患者(其中活动期19例、非活动期17例)和20例正常对照者外周血单个核细胞产生IFN-γ、IL-4和IL-10水平。结果:活动期斑秃患者外周血单个核细胞产生IFN-γ水平显著高于正常对照和非活动期患者(P<0.05),非活动期患者比正常对照者明显增高(P<0.05);活动期患者产生IL-4水平明显低于正常对照组(P<0.05),也低于非活动期患者,但差异无统计学意义(P>0.05),非活动期患者和正常对照组相比明显降低(P<0.05);活动期患者产生IL-10水平显著低于正常对照组和非活动期患者(P<0.05),非活动期患者与正常对照相比明显降低(P<0.05)。结论:斑秃患者体内可能存在Th1型细胞因子占优势,Th1型细胞因子如IFN-γ在斑秃的免疫发病中起到重要作用,并且与病情活动性有关联。

Analysis of Th1/Th2 Response Pattern for Erythrodermic Psoriasis

As one of the most serious types of psoriasis, pathogenesis of erythrodermic psoriasis（EP） is unclear so far. In this study, we aimed to detect the levels of Th1/Th2 cytokine-associated transcription factors and T-lymphocyte clone in peripheral blood mononuclear cells（PBMCs） derived from EP patients, and gene expression level of T-bet/GATA-3 in skin lesion. The potential role of Th1/Th2 reaction pattern played in the pathogenesis of EP was also discussed. Serum levels of IFN-γ, IL-2, IL-4 and IL-10 were quantified by ELISA among 16 EP patients, 20 psoriasis vulgaris（PV） patients and 15 healthy controls. The expression levels of T-bet/GATA-3 in the skin lesion and PBMCs were examined by real-time qPCR. The ratio of Th1/Th2 was measured by flow cytometry. The levels of IFN-γ, IL-2, IL-4 and IL-10 were higher in EP patients than in the healthy controls. The levels of IL-4 and IL-10 were 69.44±11.45 and 12.62±4.57 pg/mL, respectively, in EP patients, significantly higher than those in PV patients and healthy controls（P〈0.05）. Flow cytometry revealed the levels of both Th1 and Th2 in PBMCs from EP patients were higher than those in healthy controls, and the Th1/Th2 ratio was dramatically lower than in PV patients（P〈0.01）. The ratios of IFN-γ/IL-4 and T-bet/GATA-3 in EP patients were both less than 1.0, suggesting a reversal when compared with the other two groups. Our study indicated that the EP patients exerted a Th1/Th2 bidirectional response pattern, and the balance of Th cell subsets inclines to Th2, which might be one of the important mechanisms of EP pathogenesis.

Duchesnea Phenolic Fraction Inhibits Tumor Growth through Restoring the Th1/Th2 Balance in U14 Cervical Cancer Bearing Mice

Duchesnea indica (Andr.) Focke has been traditionally used to treat cancer in Asian countries for centuries. In the present study, transplanted U14 cervical cancer mouse model was used to evaluate the antitumor and immunomodulatory activity of Duchesnea phenolic fraction (DPF). ELISA and RIA assay were employed to measured the serum concentration of Th1/Th2 cytokines (IL-2, IL-4, IFN-γ and TNF-α). Administration with 0.25 g/kg, 0.5 g/kg and 1 g/kg DPF significantly reduced the tumor weight by 34.37%, 43.89% and 56.28%, respectively, as compared to the tumor control group. Furthermore, the serum level of IL-2, IFN-γ and TNF-α increased and IL-4 level decreased in a dose-dependent manner during DPF treatment, indicating that the antitumor activity of DPF may be associated with the decrease of TNF-α level and restoration of the balance of Th1/Th2 cell responses. These data suggested that DPF, a mixture of plant polyphenols, had potent anticancer activity which was in part accomplished by its immunomodulatory ability.

Activation of natural killer T cells contributes to Th1 bias in the murine liver after 14 d of ethinylestradiol exposure

BACKGROUND As the main component of oral contraceptives(OCs),ethinylestradiol(EE)has been widely applied as a model drug to induce murine intrahepatic cholestasis.The clinical counterpart of EE-induced cholestasis includes women who are taking OCs,sex hormone replacement therapy,and susceptible pregnant women.Taking intrahepatic cholestasis of pregnancy(ICP)as an example,ICP consumes the medical system due to its high-risk fetal burden and the impotency of ursodeoxycholic acid in reducing adverse perinatal outcomes.AIM To explore the mechanisms and therapeutic strategies of EE-induced cholestasis based on the liver immune microenvironment.METHODS Male C57BL/6J mice or invariant natural killer T(iNKT)cell deficiency(Jα18-/-mice)were administered with EE(10 mg/kg,subcutaneous)for 14 d.RESULTS Both Th1 and Th2 cytokines produced by NKT cells increased in the liver skewing toward a Th1 bias.The expression of the chemokine/chemokine receptor Cxcr6/Cxcl16,toll-like receptors,Ras/Rad,and PI3K/Bad signaling was upregulated after EE administration.EE also influenced bile acid synthase Cyp7a1,Cyp8b1,and tight junctions ZO-1 and Occludin,which might be associated with EEinduced cholestasis.iNKT cell deficiency(Jα18-/-mice)robustly alleviated cholestatic liver damage and lowered the expression of the abovementioned signaling pathways.CONCLUSION Hepatic NKT cells play a pathogenic role in EE-induced intrahepatic cholestasis.Our research improves the understanding of intrahepatic cholestasis by revealing the hepatic immune microenvironment and also provides a potential clinical treatment by regulating iNKT cells.

The relationship between Th1/Th2-type cells and disease activity in patients with systemic lupus erythematosus

Obejctive To investigate the imbalance of Th1/Th2 type cytokines in patients with systemic lupus erythematosus (SLE) and its relation to disease activity Methods Intracellular cytokines were determined by flow cytometry following whole blood culture Results Patients with systemic lupus erythematosus disease activity index (SLEDAI) >10 had statistically significantly fewer CD4 + or CD8 + T cells producing IFN γ than patients with SLEDAI =0, SLEDAI 1-10 or healthy controls ( P <0 01, P <0 01 or P <0 05, respectively) Patients with SLEDAI>10 also had decreased ratio of IFN γ/IL 4 positive CD4 + or CD8 + T cells, compared with patients with SLEDAI =0, SLEDAI 1-10 or healthy controls ( P <0 05) The decreased Th1 or Tc1 cells and the ratios of IFN γ: IL 4 positive CD4 + T cells were significantly correlated with disease activity ( P <0 05) Conclusion SLE is characterized by an imbalance of Th1/Th2 and Tc1/Tc2 cytokines The decreased Th1 or Tc1 cells and the Th1/Th2 ratio are related to disease activity

Expression of IL-4 and IFN-γ mRNA in PBMC of chronic hepatitis B individuals

Objective: To establish the relationship between hepatic inflammation activity and Th1/Th2 phenotype cytokines (IFN-γ, IL-4) and to investigate the fore of these cytokines as immunoregulator in inflammation activity of chronic hepatitis B. Methods: The expression of the mRNA of IL-4 and IFN-γin periphery blood monocytes (PBMC) in patients with chronic hepatitis B was determined by reverse transcription polymena chain reaction (RT-PCR) test. Results: mHNA of neither IL-4 nor IFN-γ was detected in quiescent stage, and the expression rate of IFN-γ mRNA was conspicuously higher in active stage than in convalescent stage (P < 0.05, 100% vs 50% ), while the reverse is true for the expression rate of IL-4 mrNA in convalescent stage (P < 0.05, 87% vs 13%; ). Conclusion: In patients with chronic hepatitis B, IFN-γand IL-2 serve as positive immunoregulatory cytokines, and IL-4 serves as a negative immunoregulator in HBV pathogenesis. These results indicate that Th1 phenotype cytokines up-regulate and Th2 phenotype cytokines down-regulate hepatic inflammation in chronic hepatitis B.

Correlation of serum nutrient levels with immune cell differentiation and inflammatory response activation in children with pneumonia

Objective:To investigate the correlation of serum nutrient levels with immune cell differentiation and inflammatory response activation in children with pneumonia.Methods:200 children with pneumonia who were treated in our hospital between April 2015 and August 2017 were selected as the pneumonia group, and 100 healthy children who were vaccinated in this hospital during the same period were selected as the normal control group. The differences in serum levels of nutrients, Th1/Th2 cytokines, Th17/Treg cytokines and inflammatory mediators were compared between the two groups. Pearson test was used to assess the relationship between serum nutrient levels and disease severity.Results: Serum Vit A, Fe and Zn levels of pneumonia group were lower than those of control group. The differences in serum Vit D, Ca and Mg levels were not statistically significant between the two groups of children. Serum Th1 cytokines IL-2 and TNF-β contents of pneumonia group were lower than those of control group whereas Th2 cytokines IL-4 and IL-5 contents were higher than those of control group;Th17 cytokines IL-17, IL-21 and IL-22 contents were higher than those of control group whereas Treg cytokines IL-10 and TGF-β contents were lower than those of control group;inflammatory mediators CRP, PCT and MCP-1 contents were significantly higher than those of control group. Pearson test showed that serum nutrients Vit A, Fe and Zn levels in children with pneumonia were directly correlated with the degree of immune cell differentiation and inflammatory response.Conclusion: Serum Vit A, Fe, Zn and other nutrient levels abnormally decrease in children with pneumonia, and the specific level are directly correlated with the severity of the disease.

T-bet, GATA-3 and Foxm1 expression in chronic sinusitis mucosa and their correlation with inflammatory molecule expression

Objective: To study the T-bet, GATA-3 and Foxm1 expression in chronic sinusitis mucosa and their correlation with inflammatory molecule expression. Methods: Patients with sinusitis and deflection of nasal septum who received nasal endoscopic surgery in Shengli hospital between June 2015 and February 2017 were selected and enrolled in CRS group and control group respectively. The nasal mucosa tissue was collected during operation to determine the mRNA expression of T-bet, GATA-3 and Foxm1 as well as the protein expression of inflammatory molecules. Results: T-bet, GATA-3 and Foxm1 mRNA expression as well as IL-1β, IFN-γ, TNF-α, IL-4, IL-5, IL-19, IL-20R1, IL-20R2, MMP2, MMP9, PI3K, Akt, GSK-3β and p38MAPK protein expression in nasal mucosa tissue of CRS group were significantly higher than those of control group;T-bet, GATA-3 and Foxm1 mRNA expression in nasal mucosa tissue of patients with CRS were positively correlated with IL-1β, IFN-γ, TNF-α, IL-4, IL-5, IL-19, IL-20R1, IL-20R2, MMP2, MMP9, PI3K, Akt, GSK-3β and p38MAPK protein expression. Conclusions: The high expression of T-bet, GATA-3 and Foxm1 in chronic sinusitis mucosa tissue can activate Th1 and Th2 immune response and cause mucosal inflammatory response.

Exposure to ephedrine attenuates Th1/Th2 imbalance underlying OVA-induced asthma through airway epithelial cell-derived exo-somal lnc-TRPM2-AS

Although various anti-inflammatory medications,such as ephedrine,are employed to manage cough-variant asthma,their underlying mechanisms are yet to be fully understood.Recent studies suggest that exosomes derived from airway epithelial cells(AECs)contain components like messenger RNAs(mRNAs),micro-RNAs(miRNAs),and long noncoding RNA(lncRNA),which play roles in the occurrence and progression of airway inflammation.This study investigates the influence of AEC-derived exosomes on the efficacy of ephedrine in treating cough-variant asthma.We established a mouse model of asthma and measured airway resist-ance and serum inflammatory cell levels.Real-time polymerase chain reaction(RT-qPCR),Western blotting,and enzyme-linked im-munosorbent assay(ELISA)analyses were used to assess gene and protein expression levels.Exosomes were isolated and character-ized.RNA immunoprecipitation(RIP)and RNA pull-down assays were conducted to examine the interaction between hnRNPA2B1 and lnc-TRPM2-AS1.In the ovalbumin(OVA)-challenged mouse model,ephedrine treatment reduced inflammatory responses,air-way resistance,and Th1/Th2 cell imbalance.Exosomes from OVA-treated AECs showed elevated levels of lnc-TRPM2-AS1,which were diminished following ephedrine treatment.The exosomal lnc-TRPM2-AS1 mediated the Th1/Th2 imbalance in CD4^(+)T cells,with its packaging into exosomes being facilitated by hnRNPA2B1.This study unveils a novel mechanism by which ephedrine ameli-orates OVA-induced CD4^(+)T cell imbalance by suppressing AEC-derived exosomal lnc-TRPM2-AS1.These findings could provide a theoretical framework for using ephedrine in asthma treatment.