1.Current understanding of Th2 cell differentiation and function.
Zhenhu LI ; Yuan ZHANG ; Bing SUN
Protein & Cell 2011;2(8):604-611
Helper T cell (Th) has been identified as a critical immune cell for regulating immune response since 1980s. The type 2 helper Tcell (Th2), characterized by the production of interleukin-4 (IL-4), IL-5 and IL-13, plays a critical role in immune response against helminths invading cutaneous or mucosal sites. It also has a functional role in the pathophysiology of allergic diseases such as asthma and allergic diarrhea. Currently, most studies have shed light on Th2 cell function and behavior in specific diseases, such as asthma and helminthes inflammation, but not on Th2 cell itself and its differentiation. Based on different cytokines and specific behavior in recent research, Th2 cell is also regarded as new subtypes of T cell, such as IL-9 secreting T cell (Th9) and CXCR5(+) T follicular helper cells. Here, we will discuss the latest view of Th2 cell towards their function and the involvement of Th2 cell in diseases.
Animals
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Asthma
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immunology
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metabolism
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Cell Differentiation
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physiology
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Humans
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Interleukin-9
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metabolism
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Th2 Cells
;
cytology
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immunology
;
metabolism
2.Upregulation of IL-18 expression in blood CD4+ Th2 cells of patients with allergic rhinitis.
Junling WANG ; Huanzhang SHAO ; Ling YE ; Yijie ZHANG ; Bingyu QIN
Chinese Journal of Cellular and Molecular Immunology 2023;39(12):1100-1107
Objective To investigate the expressions of IL-18, IL-18 binding protein isoform a (IL-18BPa) and IL-18 receptor α (IL-18Rα) in blood CD4+ Th2 cells of patients with allergic rhinitis (AR) and the effects of allergens on their expressions. Methods Blood samples of AR patients and healthy control subjects (HCs) were collected. Peripheral blood mononuclear cells (PBMCs) and CD4+ T cells sorted by immunomagnetic beads were stimulated by crude extract of Artemisia sieversiana wild allergen (ASWE), Platanus pollen (PPE) and house dust mite extract (HDME). Flow cytometry was used to detect the expression of IL-18, IL-18BPa and IL-18Rα in CD4+ Th2 cells, and BioPlex was used to detect the level of plasma IL-4 and analyze its correlation with the proportion of IL-18+ Th2 cells. Results Compared with HCs, the proportion of IL-18+ cells was increased in Th2 cells of AR patients; MFI of IL-18 was increased, while that of IL-18Rα was decreased. Moreover, allergens induced IL-18 and IL-18Rα expression in sorted CD4+ Th2 cells of HCs and induced IL-18Rα in that of AR patients. Additionally, elevated plasma IL-4 level was found in AR patients, which was moderately correlated with the percentage of IL-18+ Th2 cells. Conclusion Allergens may be involved in the pathogenesis of AR by inducing expression of IL-18 in peripheral blood CD4+ Th2 cells.
Humans
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Th2 Cells
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Interleukin-18/metabolism*
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Up-Regulation
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Leukocytes, Mononuclear/metabolism*
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Interleukin-4/metabolism*
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Rhinitis, Allergic/metabolism*
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Allergens
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Cytokines/metabolism*
3.Analysis of the associations of chemokine receptors expression on circulating Tfh2 and Th2 cells with sIgE level and disease severity in patients with AR.
Nan WANG ; Yin YAO ; Cai Ling CHEN ; Zhi Chao WANG ; Zheng LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(4):418-424
Objective: To clarify the chemotactic characteristics of type 2 helper T cells (Th2 cells) and type 2 follicular helper T cells (Tfh2 cells) in peripheral blood of patients with allergic rhinitis (AR), and to explore the associations between the chemokine receptors expression and the levels of antigen-specific IgE (sIgE) and the severity of the disease. Methods: The peripheral blood mononuclear cells of 41 patients with AR (20 males and 21 females, aged 35.0 (24.5, 47.0) years) and 42 healthy controls (24 males and 18 females, aged 35.0 (24.8, 46.5) years) treated in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from April 2017 to February 2018 were isolated. The expressions of chemokine receptor (CCR)2, CCR3, CCR4, CCR5, CCR7, CCR8, chemokine C-X3-C-motif receptor 1 (CX3CR1) and C-X-C motif receptor 4 (CXCR4) in Th2 and Tfh2 cells were explored by fluorescence activated cell sorting (FACs). The relationship between the expression of these chemokine receptors in Th2 cells and Tfh2 cells and the levels of serum sIgE and the scores of visual analogue scale (VAS) was analyzed. Graphpad prism 7.0 software was used for statistical analysis. Results: The significant differences in chemotactic characteristics between Th2 cells and Tfh2 cells in the control group were found: Th2 cells highly expressed chemokine receptors CCR2, CCR3, CCR5, CCR8 and CX3CR1, while Tfh2 cells highly expressed immune cell homing chemokine receptors CCR7 and CXCR4. AR patients, compared to the control, expressed higher levels of CCR2, CCR5 and CX3CR1 on peripheral Th2 cells(all P<0.01). At the same time, the proportion of CCR2+and CCR5+Th2 cells was positively correlated with VAS score (r value was 0.58 and 0.61, respectively, both P<0.01). In AR patients, higher expression levels of CCR7 on Tfh2 cells were detected (P<0.01), and the proportion of CCR7+Tfh2 cells was positively correlated with the level of serum sIgE (r=0.51, P<0.01). Conclusion: The percentage of CCR2+ and CCR5+ Th2 cells in peripheral of AR patients can reflect the severity of AR to some extent, while the percentage of CCR7+ Tfh2 cells is positively correlated with the level of serum sIgE.
Adult
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Female
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Humans
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Leukocytes, Mononuclear
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Male
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Middle Aged
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Rhinitis, Allergic/metabolism*
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Severity of Illness Index
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Th2 Cells
4.Significance of Tim-3 and Its Ligand Galectin-9 in Th1/Th2 Imbalance in Patients with Multiple Myeloma.
Rui ZHANG ; Shuang CHEN ; Ting-Ting LUO ; Jian-Hua QU
Journal of Experimental Hematology 2023;31(6):1764-1770
OBJECTIVE:
To investigate the significance of Tim-3 and Galectin-9 in Th1/Th2 imbalance in patients with multiple myeloma (MM).
METHODS:
55 newly diagnosed MM patients and 20 healthy controls were included. Flow cytometry was used to detect the expression of Tim-3 on CD4+T cells, the proportion of Th1, Th2, Tim-3+Th1 and Tim-3+Th2 cells in peripheral blood. ELISA was used to detect the levels of cytokines IFN-γ and IL-4 in serum, and PCR was used to detect the level of Galectin-9 mRNA. Then the correlations between Galectin-9 mRNA expression and Th-cell subsets and related cytokine levels, as well as the relationship between Tim-3+Th1/Tim-3+Th2 ratio and corresponding clinical features were analyzed.
RESULTS:
Compared with the control group, the expression of Tim-3 on CD4+T cells in peripheral blood of MM patients was significantly increased (P<0.05), the proportions of Tim-3+Th1 cells, Tim-3+Th2 cells and Tim-3+Th1/Tim-3+Th2 ratio in MM patients were also increased (P<0.05), while the proportion of Th1 cells and Th1/Th2 ratio in MM patients were significantly decreased (P<0.05). The level of cytokine IFN-γ and IFN-γ/IL-4 ratio in MM patients were significantly decreased (P<0.05), while the level of cytokine IL-4 was increased (P<0.05). The mRNA levels of Galectin-9 in MM patients were significantly increased (P<0.05). The levels of Galectin-9 mRNA were positively correlated with Tim-3+CD4+T cells (r=0.663), Tim-3+Th2 cells (r=0.492) and IL-4 (r=0.470), while negatively correlated with IFN-γ (r=-0.593). The ratios of Tim-3+Th1/Tim-3+Th2 in MM patients were positively correlated with ISS stage (r=0.511), osteolytic damage (r=0.556) and chromosome abnormality (r=0.632).
CONCLUSION
These results suggest that Tim-3 and Galectin-9 are involved in Th1/Th2 imbalance in MM patients, and the high ratio of Tim-3+Th1/Tim-3+Th2 is associated with poor clinical prognosis.
Humans
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Cytokines/metabolism*
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Galectins/metabolism*
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Hepatitis A Virus Cellular Receptor 2/metabolism*
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Interleukin-4/metabolism*
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Ligands
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Multiple Myeloma/metabolism*
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RNA, Messenger/metabolism*
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Th1 Cells/metabolism*
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Th2 Cells/metabolism*
5.The Levels of Inflammatory Regulatory Factors in Acute Leukemia Complicated by Infection and Its Clinical Significance.
Wen-Fang ZHANG ; Ying XU ; Qing-Ping GAO ; Han-Wen MAO ; Bo XU ; Hui QU
Journal of Experimental Hematology 2022;30(2):435-440
OBJECTIVE:
To explore the expression levels and clinical significance of helper T cell 1/helper T cell 2 (Th1/Th2) cytokine and interleukin-6 (IL-6) in patients with acute leukemia (AL) complicated by infection.
METHODS:
68 patients with AL complicated by infection admitted to Wuhan Fifth Hospital from May 2017 to January 2020 were enrolled as study group, 50 AL patients without infection were enrolled as AL group, and 30 healthy volunteers checked in physical examination center were enrolled as healthy control group. The levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10), and peripheral blood Th1/Th2 cells subsets were measured and compared among the three groups. The serum IL-6, IL-10, TNF-α and Th1/Th2 were compared between the patients with mild to moderate infection (n=52) and septic shock (n=16). The relationship between IL-6, IL-10, TNF-α, Th1/Th2 and AL infection was analyzed.
RESULTS:
The levels of IL-6, IL-10 , TNF-α, and the proportion of Th2 of the patients in study group and AL group were significantly higher than those in healthy control group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in healthy control group (P<0.001). The levels of IL-6, IL-10 and TNF-α, and the proportion of Th2 the patients in study group were significantly higher than those in AL group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in AL group (P<0.001). The serum IL-6, IL-10 and TNF-α level of the patients in septic shock group were significantly higher than those in mild-to-moderate infection group (P<0.001), while Th1/Th2 was lower than those in mild-to-moderate infection group (P<0.001). The results of ROC curve analysis showed that the area under the ROC curve (AUC) values of IL-6, IL-10, TNF-α and Th1/Th2 alone for the diagnosis of septic shock were 0.779, 0.761, 0.724 and 0.718, which were lower than that their combination (0.910) (P<0.05).
CONCLUSION
The levels of serum IL-6, IL-10 and TNF-α are high in patients with AL complicated infection and septic shock, while Th1/Th2 cell subsets is low. The combined detection of serum IL-6, IL-10, TNF-α and Th1/Th2 is a good diagnostic value for predicting the occurrence of severe septic shock.
Cytokines/metabolism*
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Humans
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Interleukin-10
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Interleukin-6/metabolism*
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Leukemia/metabolism*
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Shock, Septic/metabolism*
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Th1 Cells/metabolism*
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Th2 Cells/metabolism*
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Tumor Necrosis Factor-alpha/metabolism*
6.Effect of integrated traditional Chinese and Western medicine on Th1/Th2 cytokines level in children with asthma.
Guohua HU ; Ming LIN ; Yiji CHANG
China Journal of Chinese Materia Medica 2010;35(24):3386-3388
OBJECTIVETo discuss the effect of integrated traditional Chinese and Western medicine on Th1/Th2 cytokines level in children with asthma.
METHODChildren with asthma were randomly divided into control group and treatment group. The control group was given Montelukast Sodium tablets for 4 mg (2-5 years old) or 5 mg (6-14 years old), once every night before sleeping. At the same time, the treatment group was given Pingchuan water decoction additionally for one tie per day, in four to six-divided doses for eight weeks. On the other hand, groups of health children were selected as blank control. Before and after treatment, the level of IL-4, IL-13 and IFN-gamma were detected by elisa from 3 mL of venous blood.
RESULTBefore treatment, IL-4 and IL-13 in two groups were obviously higher than healthy group, but IFN-gamma was lower (P < 0.01, P < 0.05). After eight weeks, IL-4 and IL-13 in treatment group went down, but IFN-gamma increased. And there were significant different compared with the control group (P < 0.05).
CONCLUSIONTreating children asthma by integrated traditional Chinese and western medicine can obviously reduce IL4 and IL-13, increase IFN-gamma, and therefore lighten the airway inflammation, prevent asthma attacks effectively.
Adolescent ; Asthma ; drug therapy ; immunology ; metabolism ; Child ; Cytokines ; metabolism ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Th1 Cells ; drug effects ; metabolism ; Th2 Cells ; drug effects ; metabolism ; Western World
7.The relationship of the expression of thymic stromal lymphopoietin in nasal polyps tissues and Th2 inflammatory response.
Yu ZHONG ; Yunqiu LI ; Xuping XIAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2014;28(11):817-820
OBJECTIVE:
To explore the relationship of the expression of thymic stromal lymphopoietin (TSLP) in nasal polyps tissues and the Th2 inflammatory response.
METHOD:
Sixty patients with nasal polyps were collect ed. The immunohistochemical staining method was used to detect the expression of TSLP in nasal polyps tissues and ELISA method to the expression of IL-4, IL-5, IFN-gamma, IL-13 and analyzed the correlation between them.
RESULT:
The expression of TSLP in nasal polyp tissues was higher than that in normal inferior turbinate mucosa (P < 0.05). The expression level of IL-4, IL-5, IFN-gamma and IL-13 in nasal polyps tissues were significantly higher than those in control group (P < 0.05). TSLP staining was a statistically significant positive correlation with IL-4, IL5 and IL-13 (r = 0.475, 0.594 and 0.582, respectively, P < 0.01), while inverse correlation with IFN-gamma (r = -0.614, P < 0.01).
CONCLUSION
The high expression of TSLP might promote T cell differentiation towards Th2, and participated in the occurrence/development of nasal polyps, aggravated the nose Th2 inflammatory response.
Adult
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Cytokines
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metabolism
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Female
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Humans
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Interferon-gamma
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metabolism
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Interleukin-13
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metabolism
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Interleukin-4
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metabolism
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Interleukin-5
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metabolism
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Male
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Nasal Polyps
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immunology
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metabolism
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Th2 Cells
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immunology
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Young Adult
8.Research on different expressions of peripheral blood Th1/Th2 cells in psoriasis patients of blood heat syndrome and of blood stasis syndrome.
Jie CHEN ; Xiao-Xiao CAO ; Rong XU ; Xin LI ; Fu-Lun LI ; Bin FAN ; Yi-Fei WANG ; Feng LI ; Bin LI
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(1):46-50
OBJECTIVETo explore the correlation between the pathogenesis of psoriasis patients of blood heat syndrome (BHS) and blood stasis syndrome (BSS) and peripheral blood Th1/Th2 cells axis drift, and to observe different expressions of peripheral blood Th1/Th2 cells between healthy subjects and psoriasis patients of BHS and BSS.
METHODSThere were 15 patients in the BHS group and 15 in the BSS group. There were 16 patients in the healthy control group. The expressions of CD4+ gamma-interferon (IFN-gamma) and interleukin-4 (IL-4) in the peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry (FACS). The Th1 main cytokines such as IFN-gamma and Th2 cytokines such as IL-4 in the serum of psoriasis patients of different syndromes were detected by enzyme-linked immunosorbent assay (ELISA). The Psoriasis Area and Severity Index score (PASI) were conducted.
RESULTSFACS results showed that the expression level of CD4+ IFN-gamma+ in the PBMCs was significantly higher in the BHS group than in the BSS group and the healthy control group (P < 0.05). Besides, it was positively correlated with the PASI (P < 0.05). ELISA results showed that the peripheral serum level of IFN-gamma was significantly higher in the BHS group than in the BSS group and the healthy control group (P < 0.05). The plasma level of IFN-gamma was positively correlated with the PASI score in the BHS group (P < 0.05). The plasma level of IFN-gamma was negatively correlated with the PASI score in the BSS group (P < 0.05). The peripheral serum level of IL-4 was significantly lower in the BHS group than in the BSS group and the healthy control group (P < 0.05).
CONCLUSIONSPeripheral Th1 cells had dominant state in psoriasis patients of BHS. When psoriasis patients of BHS were transformed to BSS or to the normal level, the expression of peripheral blood Th1 cells decreased.
Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Psoriasis ; blood ; diagnosis ; Th1 Cells ; metabolism ; Th1-Th2 Balance ; Th2 Cells ; metabolism ; Young Adult
9.Change of the expression level of Th1 and Th2 cytokines around the xenogeneic cancellous bone scaffold after transplantation: an experiment in rabbits.
Rong-chang LEI ; Xin-chun JIAN ; Zhi-qiang QIN
Chinese Journal of Plastic Surgery 2007;23(6):507-510
OBJECTIVETo observe the dynamic immunity of the porcine cancellous bone scaffold(PCBS) after transplantation and provide experimental evidences for amending and clinical use.
METHODSThe PCBS was gained through physical and chemical disposals to porcine cancellous bone and was implanted subcutaneously in rabbit. The histological investigation and the expression of Th1 (such as IL-2, IFN-gamma) and Th2 (such as IL-4, IL-10) mRNA were measured by HE, RT-PCR respectively in 1,2,4,8,12 week postoperation.
RESULTSHE revealed: Inflammation cells (lymphocytes and monocytes) were shown abundantly in the surrounding tissue in 1 week and were decreased gradually since 2 week. At 12 week, there were few inflammation cells in the surrounding tissue. RT-PCR revealed: The mRNA expression level of Th1 cytokines such as IL-2, IFN-gamma was high in 1 week and began to fall since 2 week. At 12 week, the mRNA expression level of Th1 cytokines was low; The mRNA expression level of Th2 cytokines such as IL-4, IL-10 was low in 1 week, rose gradually since 2 week and reached tiptop in 8 week. At 12 week, the mRNA of Th2 cytokines maintained high level expression.
CONCLUSIONSThe porcine cancellous bone scaffold excitate immunoreaction was transitory inflammation after implantation.
Animals ; Bone Transplantation ; immunology ; Cytokines ; metabolism ; RNA, Messenger ; genetics ; Rabbits ; Swine ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism ; Tissue Scaffolds ; Transplantation, Heterologous
10.Study on Th1/Th2 transcriptional regulatory mechanism of san'ao tang in bronchial asthmatic rats.
China Journal of Chinese Materia Medica 2012;37(9):1324-1326
OBJECTIVETo study the regulatory effect of San'ao Tang on Thl/Th2 cells and its interference on transcription factor GATA-3 and T-bet-mRNA in asthmatic rats.
METHODRat asthma model was established by abdominal injection and aerosol inhalation of OVA. The content of cytokines IL-4 and IFN-gamma in alveolus lavage fluid of asthmatic rats was detected before and after the oral administration with large, medium, low dose of San'ao Tang and dexamethasone. T-bet and GATA-3 mRNA expressions in lung tissues were determined by RT-PCR.
RESULTCompared with other groups, the medium-dose group showed a notable decrease in IL-4 in rat BALF and an increasing IFN-gamma. Its IL-4/IFN-gamma is significant lower than the asthma group, with expressions of lung tissue GATA-3 and transcription factor T-bet-mRNA in line with changes in IL-4 and IFN-gamma.
CONCLUSIONSan'ao Tang may have a inhibitory effect on airway inflammation of asthmatic rats by regulating Th1/Th2 transfer factors.
Animals ; Asthma ; drug therapy ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Th1 Cells ; drug effects ; metabolism ; Th2 Cells ; drug effects ; metabolism