Mechanism of the expression of IL-25 in the lung during asthma / 西安交通大学学报(医学版)

Objective To study the molecular mechanism of interleukin 25 (IL-25)expression in the lung of asthmatic rats.Methods The expressions of IL-25 mRNA and protein in the lungs were detected by Real-time PCR and ELISA,respectively.The levels of IL-25 mRNA and protein were detected by ovalbumin (OVA)in human bronchial epithelial cells.And the transcription factors that regulate IL-2 5 expression were explored through site prediction.Results The expressions of IL-25 mRNA and protein in the lung of OVA-induced asthma rats were significantly increased during animal experiments.Cell experiments showed that OVA could increase the expression of IL-2 5 in human bronchial epithelial cells in a dose-dependent manner,and OVA could upregulate the expression of transcription factor AP1.AP1 was found in the promoter region of IL-25 by site prediction.The AP1 inhibitor (T5224)significantly reduced the expression of IL-25 in OVA-induced human bronchial epithelial cells. Conclusion The molecular mechanism of IL-25 expression induced by OVA in asthma is related to the increase of transcription factor AP1 .

Expression of IL-25 and IL-33 and the count of EOS in peripheral blood of children with allergic rhinitis receiving immunotherapy / 临床耳鼻咽喉头颈外科杂志

OBJECTIVES@#To investigate the expression of IL-25,IL-33 and EOS in children with allergic rhinitis (AR).@*METHODS@#Ninety-four AR children receiving immunotherapy and 23 healthy people were concluded in the study. The serum levels of IL-25 and IL-33 were detected by Enzyme-linked Immunosorbent Assay (ELISA), and a count of EOS were measured.@*RESULTS@#The serum levels of IL-25 and IL-33 in the mild group were higher than control group (0.05). The serum levels of IL-25 and IL-33 in the severe group were higher than those in mild group (<0.05). The serum levels of IL-25 and IL-33 in the severe group were higher than control group (<0.05). The count of EOS in the severe group were higher than those in mild group (<0.05). The count of EOS in the severe group were higher than those in control group (<0.05). Spearman test showed the serum levels of IL-25 in the children with AR patients have positive correlation with the serum levels of IL-33 (<0.05, =0.238).@*CONCLUSIONS@#Expression of IL-25 levels, IL-33 levels and the count of EOS in patients with AR are enhanced, which shows that IL-25, IL-33 and the count of EOS are involved in the AR. If we can understand the mechanism of them, it will profound implications for treatment.

IL-25 blockade inhibits metastasis in breast cancer

Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumor-infiltrating CD4 T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.

Allergen-Dependent Differences in ILC2s Frequencies in Patients With Allergic Rhinitis

PURPOSE: Group 2 innate lymphoid cells (ILC2s) are a novel population of lineage-negative cells that induce innate type 2 responses by producing the critical Th2-type cytokines IL-5 and IL-13 in response to IL-25 and IL-33 stimulation. ILC2s accumulation in the peripheral blood of patients with allergic rhinitis (AR) is controversial; the precise role of ILC2s in the immunopathogenesis of AR is still not clear. We investigated the role of ILC2s in phenotypic AR sensitized to distinct allergens. METHODS: Flow cytometric analysis of the peripheral blood of 7 healthy controls (HCs), 9 patients monosensitized to house dust mite (HDM), and 8 patients monosensitized to mugwort was performed to quantify ILC2s frequency. Peripheral blood mononuclear cells (PBMCs) were isolated from HDM-AR and mugwort-AR patients, and Lineage- and Lineage+ cells were separated using a fluorescence-activated cell sorter (FACS). IL-5 and IL-13 levels in the supernatants of PBMCs, and Lineage- and Lineage+ cells stimulated with IL-25 and/or IL-33 combined with IL-2 in vitro were assessed using the Milliplex magnetic bead kit. RESULTS: The percentage of ILC2s was significantly elevated in HDM-AR patients compared to mugwort-AR patients and HCs, while no significant difference was found between mugwort-AR patients and HCs. IL-33+/-IL-25 plus IL-2 induced a significantly greater release of IL-5 and IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. IL-25 plus IL-2 also induced a significantly greater release of IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. Stimulation with IL-33 and/or IL-25 combined with IL-2 also induced a significantly greater IL-5 and IL-13 release from Lineage- cells compared to Lineage+ cells. CONCLUSIONS: AR patients sensitized to HDM or mugwort allergen have distinct phenotypic and functional profiles in ILC2s frequencies. ILC2s mediate major type 2 immunity in the development of HDM-AR and may be a potential therapeutic target.

Regulation of IgE-Mediated Food Allergy by IL-9 Producing Mucosal Mast Cells and Type 2 Innate Lymphoid Cells

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.

Clinical Characteristics and Expression Pattern of IL-33 and IL-25 According to Histologic Classification in Chronic Rhinosinusitis with Nasal Polyposis

BACKGROUND AND OBJECTIVES: Many kinds of inflammatory cells and cytokines are suggested to be related to the pathophysiology of chronic rhinosinusitis with nasal polyposis (CRSwNP), but not yet fully understood. The objectives of this study were to classify CRSwNP patients according to histologic features and to reveal the roles of IL-33 and IL-25, on the pathophysiology of CRSwNP. MATERIALS AND METHOD: CRSwNP patients (n=122) were divided into 3 groups according to the type of nasal polyp; eosinophilic polyp (EP, n=38), neutrophilic polyp (NeuP, n=15) and non-eosinophilic non-neutrophilic polyp (NENN, n=63) groups. Clinical features and the expressions of IL-25 and IL-33 were evaluated among the groups. RESULTS: The EP group showed many clinical features that were different from the other groups: increased prevalence of asthma and olfactory dysfunction, increased percentage of blood eosinophils, increased E/M ratio, and poor postoperative outcomes such as recurrent polyposis and the need for frequent use of oral steroids. Numbers of IL-33 and IL-25 positive cells were significantly higher in the EP group compared with the other groups in the lamina propria (p=0.001). CONCLUSION: These results suggest that patients with an eosinophilic polyp are clinically and pathogenetically different from patients with other types of polyps, and IL-25 and IL-33 are associated with the pathogenesis of chronic rhinosinusitis with eosinophilic polyps.

Effect of Asarone Injections on Expression of IL-25, Eosinophils Cationic Protein(ECP) and IL-27 in Ser-um of Asthma Patients / 中国药师

Objective:To monitor the effects of asarone injections on the expression of IL-25, IL-27 and eosinophils cationic pro-tein ( ECP) in the serum of asthma patients. Methods:Totally 100 patients with bronchial asthma were randomly divided into the ob-servation group ( 55 cases ) and the control group ( 45 cases ) . The control group was treated with the conventional symptomatic treat-ment ( oxygen inhalation, spasmolysis and anti-asthma, and anti-infection, etc) . The observation group was given asarone injections 24 mg in 250 ml 0. 9% sodium chloride infusions, once a day for 14 days on the basis of the conventional therapy. The changes in symp-toms, and pulmonary function in the patients were observed with simultaneous detection of IL-25, ECP and IL-27 levels. Results:To-tal effective rate of the observation group was 92. 7%,which was higher than that of the control group (P<0. 05). Asarone injections could decrease IL-25, ECP and IL-27 levels in the observation group compared with those in the control group with statistically signifi-cant difference (P<0. 05 or 0. 01). Conclusion:Asarone injections can decrease the levels of IL-25, IL-27and ECP in the serum of asthma patients and inhibit the formation of inflammatory cells to alleviate the symptoms of airway inflammation.

Protease-Activated Receptor 2 Is Involved in Th2 Responses against Trichinella spiralis Infection

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.