Effect Of IL-25 Induces The Airway Remodeling By Native Immune Cells In Asthma Of Mouse

BACKGROUND:Allergic asthma is an airway inflammation accompanied by increased secretion of cytokines. Infiltration of eosinophils and other cells, excessive mucus production and airway hyper-reactivity induce airway narrowing and significant morbidity. Interleukin-25(IL-25) is one of the IL-17 cytokine family members which can promote the Th2 immune responses. The interaction between IL-25 and Th2 inflammatory cytokines such as IL-4 and IL-13 was still unclear. Importantly, Nuocytes are nature helper cells without any lymphocyte markers. They exist in human and mouse liver, gut, and lung which can induce tissue repair and type-2 immune responses in airway inflammation, however, the mechanisms underlying remain unclear. Based on the previous findings, we hypothesized that IL-25 in asthma could promote the activation of nuocytes, and then induce a large amount of IL-4 and IL-13 to enhance Th2 cytokine responses and and then lead to airway remodeling which promote the occurrence and development of asthma.. The present finding indicated that IL-25 might be involved in a series of asthmatic immune response, play an important role in nuocytes population and activation to maintain Th2 central memory and sustain asthmatic inflammation and remodeling.OBJECTIVE:To study the effect of IL-25 on airway remodeling in asthma by nuocytes cells.METHODS:The mice were randomly divided into three groups:control group, asthma group, and anti-IL-25. Nuocytes cells were collected from mouse spleen and marrow of OVA-induced asthma model by density gradient centrifugation.Samples were divided into 3 groups according to different intervention conditions: control group, IL-25 group, anti-IL-25 group. Hematoxylin-eosin staining was determined the lung tissue from the pathology. The expression of IL-4 and IL-13 proteins in bronchoalveolar lavage fluid and nuocytes cells supernatant were detected by ELISA. The expression of a-SMA and collagen-â…  proteins in lung tissue were detected by Western blot and Immunohistochemistry. The expression of The expression of collagen-â…  and a-SMA mRNA was detected by RT-PCR.RESULTS1. The expression of IL-4 and IL-13 protein in asthma group was higer than that in the control group in BALF(P<0.05), no significant difference was found in the anti-IL-25 group and control group (P>0.05).2. The expression of IL-4 and IL-13 protein in IL-25 group was higer than that in the control group in nuocytes cells supernatant (P<0.05), no significant difference was found in the anti-IL-25 group and control group (P>0.05).3. The expression of a-SMA and collagen-â…  protein and mRNA in asthma group were higer than that in the control group (P<0.05), and there is no differenct in the anti-IL-25 group and control group (P>0.05).CONCLUSIONS1. Interleukin-25 can promote the expressing TH2 cytokines in asthma by nuocytes cells.2. Native immune cells in asthma of mouse may lead to airway remodeling which promote the occurrence and development of asthma.