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Objective:To observe the effect of Tongxie Yaofang on the expressions of colon serotonin transporter （SERT）， liver 5-hydroxytryptamine<sub>2A</sub> receptor （5-HT<sub>2A</sub>R） protein， serum 5-HT and inflammatory factors in ulcerative colitis （UC） model rats of liver stagnation and spleen deficiency， in order to explore the basis of syndrome of liver stagnation and spleen deficiency and the intervention mechanism of Tongxie Yaofang. Method:Fifty male SD rats were randomly divided into blank control group， model group， high， medium and low-dose Tongxie Yaofang group （10，5，2.5 g·kg<sup>-1</sup>）， and salazosulacil group （0.3 g·kg<sup>-1</sup>）. The ulcerative colitis model of liver depression and spleen deficiency was established by 2，4，6-trinitrobenzene sulfonic acid （TNBS）/ethanol solution enema + restraint stress + diet loss. After successful modeling， the samples were collected after 21 days of drug intervention. Htoxylin eosin （HE） staining and oil red staining were used to observe the pathological changes of colon and liver in each group. Serum interleukin-6 （IL-6）， IL-9， 5-HT and superoxide dismutase （SOD） were detected by enzyme linked immunosorbent assay （ELISA）. Protein expressions of SERT in the colons and 5-HT<sub>2A</sub>R in liver of rats were detected by Western blot. Result:Compared with the normal group， obvious ulcers were formed in the colon and lipid droplets in the liver increased in the model group， serum levels of IL-6， IL-9 and 5-HT in the model group increased， while the level of SOD decreased （<italic>P</italic><0.05）. The protein expression of SERT in colon decreased， whereas the protein expression of 5-HT<sub>2A</sub>R in liver increased （<italic>P</italic><0.05）. Compare with model group， the pathological damage of colon was improved， and the formation of lipid droplets in liver was reduced in high， medium-dose Tongxie Yaofang groups and sulfasalazine group. The serum levels of IL-6， IL-9 and 5-HT decreased， while the level of SOD increased in Tongxie Yaofang group and sulfasalazine group （<italic>P</italic><0.05）. The protein expression of SERT in colon increased in high，low-dose Tongxie Yaofang groups and sulfasalazine group， and the protein expression of 5-HT<sub>2A</sub>R in liver decreased in medium， low dose Tongxie Yaofang groups and sulfasalazine group （<italic>P</italic><0.05）. Conclusion:Tongxie Yaofang may reduce the content of 5-HT， and regulate the intestinal motility and sensory system by up-regulating the expression of SERT in the colon， inhibit the expressions of IL-6，IL-9 and other inflammatory factors， and play an anti-inflammatory role， reduce the content of 5-HT and the expression of 5-HT<sub>2A</sub>R in the liver， increase the level of SOD， regulate emotion and lipid metabolism in the liver， and then exert the intervention effect on ulcerative colitis with liver depression and spleen deficiency on the whole.
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【Objective】 To detect the abnormal expression of Th9, Thl7, Treg cells, interleukin-9 (IL-9), interleukin-17 (IL-17) and transforming growth factor-β(TGF-β) in patients with multiple myeloma (MM), and to explore their roles in primary diagnosis of MM. 【Methods】 The level of Th9, Th17 and Treg cells in peripheral blood of 54 MM patients with(patient) and 45 healthy volunteers (control) were measured by flow cytometry, and the levels of IL-9, IL-17 and TGF-β were detected by ELISA. 【Results】 The percentages(%) of Th9, Thl7 in MM patients increased significantly in comparison to controls [1.37±0.39 vs 0.79±0.26; 2.02±0.41 vs 1.18±0.32] (P<0.05). The proportion(%) of CCD4+ CD25+ FoxP3+ Treg cells in patients was significantly lower than those in controls (4.92±0.83 vs 7.04±1.85, P<0.05). The expression levels (%) of IL-9 and IL-17 in the peripheral blood of patients were significantly higher than those in controls (25.74 1±7.33 vs 16.82±5.58; 11.01±3.71 vs 7.68 ± 2.57, P<0.05). The levels of TGF-β in patients and controls were (3.73±1.44)% vs (6.95±2.12)%, showing a significant decrease (P<0.05). 【Conclusion】 The abnormal percentage of Th9, Thl7, Treg cells and the abnormal expression levels of IL-9, IL-17, TGF-β in MM patients may play an important role in the initial diagnosis of MM.
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Objective:To study the effect of modified Erchentang on levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), interleukin-9 (IL-9), interleukin-4 (IL-4) and interleukin-13 (IL-13) in plasma and bronchoalveolar lavage fluid (BALF) of all rats, as well as expressions of interleukin-4 (IL-4) receptor (IL-4R1) and interleukin-13 (IL-13) receptor (IL-13RA1) in bronchioles tissue of rats with chronic obstructive pulmonary disease (COPD). Method:Fifty SD rats were randomly divided into 5 groups, namely normal group, model group, and low, middle and high-dose modified Erchentang groups (5, 10, 20 g·kg-1), with 10 rats in each group. COPD in rat was prepared by using cigarette smoke combined with dripping lipopolysaccharide (LPS) in trachea. After the modeling, normal and model groups were given normal saline solution through intragastric (ig) administration, while other groups were given corresponding herbal drugs (5, 10, 20 g·kg-1) intragastrically (ig) for 14 days. The levels of IL-12, IFN-γ, IL-9, IL-4 and IL-13 in plasma and BALF were detected by Enzyme-linked immunosorbent assay (ELISA) method， and immunohistochemistry (IHC) method was used to detect the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue of all of the groups. Result:Compared with the normal group, the levels of IL-12 and IFN-γ were decreased significantly (P<0.01), but the levels of IL-9, IL-4 and IL-13 in plasma and BALF were significantly increased (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were increased significantly (P<0.01) in model group. Compared with the model group, the levels of IL-12 and IFN-γ were increased significantly, while the levels of IL-9, IL-4 and IL-13 in plasma and BALF were decreased significantly (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were decreased significantly (P<0.01) in modified Erchentang groups (10, 20 g·kg-1). Conclusion:Modified Erchentang has effects in resisting inflammatory and protecting tissue structure of bronchioles. Its mechanism may be correlated with increasing the levels of IL-12, IFN-γ and reducing the levels of IL-9, IL-4 and IL-13 in plasma and BALF, and inhibiting the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue.
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As a newly identified T helper cell subset, Th9 plays an important role in anti-tumor immunity. Th9 can be differentiated from CD4+T cells that have been induced by TGF-beta and IL-4. In addition, other CD4+T helper cell subsets can be developed to Th9 cell in particular situations, thereby showing its plasticity. Results of animal experiments have indicated that Th9 inhibits tumor growth and plays a significant role in anti-tumor immunity by secreting related cytokines such as IL-9. A few cytokines and molecules can regu-late the differentiation and development of Th9 cells in different signaling pathways. This review will focus on the production, anti-tu-mor immunity, related mechanism, and signaling pathways of Th9 cells, thereby providing a new field of vision and idea for anti-tumor therapy in the future.
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Objective:To explore the effects and mechanism of anti IL-9 antibody on malignant ascites ( MA) of hepatic carci-noma in mice.Methods:A mouse model of MA was established by mouse H 22 cell line.45 mice were divided randomly into experi-mental group,negative control group and blank control group at 24 hours after modeling,with 15 mice in each group.The experimental group was injected intraperitoneally with anti IL-9 antibody;the negative control group was injected with isotype IgG antibody;the blank control group was injected with normal saline .The weight and behavior of the mice were measured before each injection .Five mice of each group was sacrificed at 24 hours after the last injection to measure the volume of MA .The level of VEGF,MMP-2,IL-9 and IFN-γin MA were determined with ELISA assay;the survival time of rest mice were recorded and compared .Results:The mean volume of MA of experimental group,negative control group and blank control group were (6.70±1.52)ml,(10.28±1.75)ml,(10.36±2.30) ml,respectively,the MA volume of experimental group were lower as compared to negative control group and blank control group ( P0.05 ) .Conclusion:Intraper-itoneal injection anti IL-9 antibody on H22 ascites-bearing mice can effectively inhibit the generation of the MA .The mechanism may be related to the inhibition of the expression of the VEGF and IL-9.
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Objective To detect the levels of helper T cells (Th) 17 and Th9 cells in the peripheral blood of patients with pedi-atric bronchial asthma and the expression of interleukin 17 (IL-17) ,IL-9 and total IgE in serum ,and to discuss their effect and clini-cal significance in pathogenesis of pediatric asthma .Methods A total of 46 children with bronchial asthma ,including asthma attack group (n=26) and asthma remission group (n=20) were selected .Healthy children were selected as healthy control group (n=20) .Flow cytometry was used to detect the percentages of Th17 and Th9 cells in the peripheral blood .The levels of IL-17 and IL-9 in serum were measured by enzyme-linked immunosorbent assay (ELISA) .Serum total IgE levels were measured by the specific protein analyzer .Results The percentages of Th17 and Th9 cells in the peripheral blood were significantly higher in asthmatic group compared with remission group and healthy control group (P<0 .05) .The percentages of Th17 and Th9 cells in the periph-eral blood was significantly higher in remission group compared with healthy control group (P<0 .05) .The levels of IL-17 ,IL-9 and total IgE in serum were significantly higher in asthmatic group compared with remission group and healthy control group (P<0 .05) .The levels of IL-17 ,IL-9 and total IgE in serum were significantly higher in remission group compared with healthy control group (P<0 .05) .The levels of IL-17 and IL-9 in serum of asthmatic children were positively correlated with total IgE levels (P<0 .05) .The correlation analysis results showed that the levels of IL-17 ,IL-9 and total IgE in serum of patients with pediatric bron-chial asthma have a positive correlation .(r=0 .717 ,0 .491 ,0 .786 ,P<0 .05) .Conclusion Th17 ,Th9 cells and their cytokines in pe-ripheral blood of patients with pediatric bronchial asthma play important roles in the pathogenesis of asthma and are positively cor-related with the severity of asthma .
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Objective:To explore the function of IL-9 and PU.1 on genesis and development of pulmonary fibrosis,and the effect of active vitamin D3[1,25(OH)2VD3] on the expression levels of this two factors during the pathogenesis of fibrosis.Methods: 90 male SD rats were randomly divided into model group,treatment group,control group (n=30).Bleomycin(5 mg/kg) was injected into the trachea of rats to establish the model of pulmonary fibrosis in the model group and treatment group,while the control group was injected with isopyknic sterile saline.The treatment group,the model group and the control group were injected intraperitoneally with active vitamin D3,solvent of vitamin D3 (propylene glycol) and sterile saline on the 2nd day after surgery respectively.All injections were carried out once every other day.10 rats were euthanized at 14th,21st and 28th day in each group in turn.After obtaining lung tissues from experimental rats,the pathological change of lung was compared by hematoxylin-eosin staining.The difference of collagen fiber and hydroxyproline content were compared by the Masson staining and basic-hydrolysis method respectively.The mRNA and protein expression of IL-9 and PU.1 in lung tissue were detected by Real-time PCR and immunohistochemical technology respectively.The expression of IL-9 in serum was detected by ELISA.Results: Fibrosis appeared in lungs of experimental rats treated with bleomycin after 14 days,and more and more aggravated with time.At three time points,the hydroxyproline content in model group and treatment group were significantly higher than that of control group,and the treatment group was significantly lower than the model group.At three time points,the expression of IL-9 and PU.1 in model group and treatment group were risen gradually,and obviously higher than that in control group.On the 14th and 21st day,the expression of two factors in treatment group was significantly lower than model group;on the 28th day,there was no statistically significant difference between treatment group and model group(P>0.05).In model group and treatment group,the expression of two factors on 21st day was significantly higher than that on 14th day;there was no statistically significant difference between the 28th day and the 21st day.Conclusion: IL-9 and PU.1 may play a profibrotic role at early stage of pulmonary fibrosis induced by bleomycin.The active vitamin D3 may lower the expression level of PU.1,and then reduce the secretion of IL-9,thus may play an inhibiting effect on genesis and development of pulmonary fibrosis in rats.
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Objective To investigate the expression and significance of Th9, Th17 and CD4+CD25+Foxp3+regulatory T (Treg) cells as well as the related cytokines (IL-9, IL-17, TGF-β) in peripheral blood of patients with adult primary immune thrombocytopenia ( ITP) . Methods Peripheral blood samples were collected from 47 patients with ITP and 39 age-and sex-matched healthy subjects. The percentages of Th9, Th17 and CD4+CD25+Foxp3+Treg cells in peripheral blood samples were detected with flow cytometry. The levels of IL-9, IL-17 and TGF-βin serum samples were detected by enzyme linked immunosorbent assay ( ELISA) . Results Compared with healthy subjects, the percentages of Th9 and Thl7 cells and the concen-trations of IL-9 and IL-17 in patients with ITP were significantly increased [(1. 27±0. 31)% vs (0. 71± 0. 26)%, P<0. 05;(2. 01±0. 42)% vs (0. 97±0. 32)%, P<0. 05. (26. 52±7. 48) ng/L vs (16. 16± 5. 27) ng/L, P<0. 05;(10. 97±3. 94) ng/L vs (7. 14±2. 73) ng/L, P<0. 05]. The percentages of CD4+CD25+Foxp3+ Treg cells and the concentrations of TGF-β in patients with ITP were lower than those in healthy subjects [(4. 69±0. 85)% vs (7. 16±1. 92)%, P<0. 05. (3. 76±1. 28) μg/L vs (6. 41±1. 83)μg/L, P<0. 05]. Moreover, the blood platelet counts in patients with ITP were negatively correlated with the percentages of Th9 and Th17 cells and the concentrations of IL-9 and IL-17 (γs=-0. 349, P=0. 037;γs=-0. 392, P=0. 031;γs=-0. 436, P=0. 014;γs=-0. 401, P=0. 027), but were positively correlated with the percentages of CD4+CD25+Foxp3+ Treg cells and the concentrations of TGF-β (γs=0. 411, P=0. 024;γs=0. 407, P=0. 026). Conclusion The imbalanced distribution of Th9, Th17 and Treg cells and the abnormal expression of related cytokines (IL-9, IL-17 and TGF-β) in patients with ITP might be the possible immunological pathogenesis of ITP.
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Due to the increasing prevalence and number of life-threatening cases, food allergy has emerged as a major health concern. The classic immune response seen during food allergy is allergen-specific IgE sensitization and hypersensitivity reactions to foods occur in the effector phase with often severe and deleterious outcomes. Recent research has advanced understanding of the immunological mechanisms occurring during the effector phase of allergic reactions to ingested food. Therefore, this review will not only cover the mucosal immune system of the gastrointestinal tract and the immunological mechanisms underlying IgE-mediated food allergy, but will also introduce cells recently identified to have a role in the hypersensitivity reaction to food allergens. These include IL-9 producing mucosal mast cells (MMC9s) and type 2 innate lymphoid cells (ILC2s). The involvement of these cell types in potentiating the type 2 immune response and developing the anaphylactic response to food allergens will be discussed. In addition, it has become apparent that there is a collaboration between these cells that contributes to an individual's susceptibility to IgE-mediated food allergy.
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Allergens , Cooperative Behavior , Food Hypersensitivity , Gastrointestinal Tract , Hypersensitivity , Immune System , Immunoglobulin E , Interleukin-9 , Lymphocytes , Mast Cells , PrevalenceABSTRACT
Objective The effectiveness of Zhuang nationality medical lotus needle plus back cupping therapy ( Zhuang needle-cupping therapy) , Flixonase aqueous nasal spray and cetirizine tablets in treating allergic rhinitis (AR) was compared for the exploration of the therapeutic mechanism of Zhuang needle-cupping therapy. Methods A total of 200 recruited AR patients were randomly divided into four groups in the proportion of 1:1:1:1. The four groups were Zhuang needle-cupping therapy group, cetirizine group, Flixonase group and blank control group. The blank control group had no medication, and the patients of the other three medication groups were given the corresponding treatment. Ten days constituted one treatment course, and interval between two courses lasted one week. After two courses, the therapeutic effect was evaluated. The changes of specific IgE (S-IgE), leukotriene (LT), interleukin 4(IL-4), IL-9 mRNA, interferon gamma (IFN-γ), Thl / Th2 cells, and Th17 cytokine ( IL-17) were observed before and after treatment. Results ( 1) After two treatment courses, Zhuang needle-cupping therapy group had better therapeutic effect than cetirizine group , Flixonase group and blank control group, and the therapeutic effect of cetirizine group and Flixonase group was better than the blank control group (P0.05). ( 2) After treatment, the levels of S-IgE, LT, IL-9 mRNA, IL-4 and IL-17 were decreased, and IFN-γ and Th1/Th2 levels were increased in the three medication groups ( P0.05). The results of inter-group comparison after treatment showed that Zhuang needle-cupping therapy group had better effect on improving S-IgE, LT, IFN-γand Th1/Th2 than cetirizine group and Flixonase group (P<0.05). (3) During the trial, no adverse reaction was found. Conclusion Zhuang needle-cupping therapy exerts certain therapeutic effect for AR, and the mechanism may be related with the inhibition of S-IgE, LT, IL-9 mRNA and IL-17 expression, and with the regulation of Th1/Th2 imbalance by decreasing TH2 cytokine level and increasing Th1 cytokine level.
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Objective To investigate the predictive value of IL-9 cytokines in the patients with acute respiratory distress syndrome (ARDS).Methods According to Berlin definition of ARDS published in 2012,data of 28 patients with ARDS and another 22 healthy subjects as control were collected for prospective study from June,2013 to July,2014.Of them,there were 23 patients with severe pneumonia,1 patient with acute mercury poisoning,2 patients with severe acute pancreatitis,2 patients with acute paraquat poisoning.The survivors of ARDS patients were followed up.The ARDS patients were divided into moderate group (n =18) and severe group (n =10) as per the severity of the disease diagnosed at the first day after admission.And the ARDS patients were also divided into non-survival group (n =15) and survival group (n =13) according to the ARDS patients survived for 28 days.Three mLs of peripheral venous blood were collected in the early morning from fasted ARDS patients on the first and the third day after diagnosis of ARDS confirmed,and those of healthy subjects were collected on the first day after admission.The IL-9 cytokine level of peripheral venous blood detected by using enzyme linked immunosorbent assay (ELISA).The comparisons of levels of IL-9 cytokine were carried out between ARDS group and control group on the first day after diagnosis of ARDS established,between moderate group and severe group on the first day and the third day,and between survival group and non-survival group.The receiver operating characteristic (ROC) curve was used to evaluate the performance of IL-9 as a prognostic indicator in the early stage of ARDS.Data were analyzed by using SPSS 19.0 software.Results On the first day after diagnosis of ARDS,there were no statistically significant differences in age,APACHE Ⅱ score,procalcitonin (PCT),C-reactive protein (CRP),white blood cell count,lactate,and albumin between survival group and non-survival group (P ＞ 0.05).PH value in non-survival group was significantly lower than that in survival group (P＜0.05).IL-9 cytokine level of peripheral venous serum in ARDS group was significantly higher than that in healthy control group (P ＜ 0.05).There were no statistically significant differences in IL-9 level of peripheral venous serum both between moderate group and severe group and between survival group and non-survival group (P ＞ 0.05).On the third day,IL-9 level in severe group was significantly higher than that in moderate group (P ＜ 0.05),and that in survival group was significantly lower than that in non-survival group (P ＜ 0.05).The ROC of IL-9 at the first day for predicting mortality had all area under curve (AUC) to be 0.579 (95％ CI 0.361-0.798,P ＞ 0.05).The ROC of IL-9 on the third day for predicting mortality had AUC of 0.769 (95％ CI 0.592-0.947,P ＜ 0.05).When the cut-off value of IL-9 for the death followed up for 28 day' s was 2.88 pg/mL,the sensitivity was 86.7％,and the specificity was 61.5％.Conclusions IL-9 levels of in patients with ARDS were significantly higher,and IL-9 level can be helpful for the assessment of ARDS severity in the early stage,and for prognosis as well.
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Among cockroaches (CR) that live in people’shomes, two species, i.e., German CR (Blattella germanica) and American CR (Periplaneta americana) predominate in temperate and tropical areas, respectively. CR is an important source of inhalant indoor allergens that sensitize atopic subjects to (localized) type I hypersensitivity or atopy including allergic rhinitis and atopic asthma. In Thailand the predominant CR species is P. americana. CR allergens are found throughout CR infested houses; the number found in kitchens correlates with the degree of CR infestation while sensitization and reactivation of the allergic morbidity are likely to occur in the living room and bedroom. Levels of the CR allergens in homes of CR allergic Thais, measured by using locally made quantification test kits, revealed that the highest levels occur in dust samples collected from the wooden houses of urban slums and in the cool and dry season. CR allergens are proteins that may be derived from any anatomical part of the insect at any developmental stage. The allergens may be also from CR secretions, excretions, body washes or frass. The proteins may be the insect structural proteins, enzymes or hormones. They may exist as dimers/multimers and/or in different isoforms. Exposure to CR allergens in infancy leads to allergic morbidity later in life. Clinical symptoms of CR allergy are usually more severe and prolonged than those caused by other indoor allergens. The mechanisms of acute and chronic airway inflammation and airway hyper-responsiveness (AHR) have been addressed including specific IgE- and non-IgEmediated mechanisms, i.e., role of proteaseactivated receptor-2 (PAR2). Participation of various allergen activated-CD4+ T cells of different sublineages, i.e., Th2, Th17, Th22, Th9, Th25, Tregs/Th3 as well as invariant NKT cells, in asthma pathogenesis have been mentioned. The diagnosis of CR allergy and the allergy intervention by CR population control are also discussed.