title: Generation of IL10 and TGFB1 coexpressed mice displaying resistance to ovalbumin-induced asthma.
abstract: Asthma is a common chronic inflammatory disease in the airways with wide prevalence, and it is thought to be caused by the combinational factors in environment and genetics. A large body of studies has suggested that cell immunity played a vital role in regulating the airway hyperreactivity (AHR) and inflammation. Therefore, we here developed a mouse model of asthma by microinjecting the pronucleus with a vector spontaneously coding human IL10 and TGFB1 gene to explore the possible interaction between these two potent molecules during asthma progression. From the total 35 newborn mice, we successfully obtained 3 founders expressing exogenous genes. In the transgenic mice, we observed profoundly enhanced expression of IL10 and TGFB1. In the condition of ovalbumin challenge, transgenic mice displayed a 1.9-fold higher MCh50 score than wild-type counterparts, indicating reminiscent AHR. Meanwhile, a three-fold decrease of cell counts in bronchoalveolar lavage fluid (BALF) was recorded as well. These results suggested that IL10 and TGFB1 cooperatively protected the respiratory system in response to antigenic stimulus. To interrogate the respective behaviors of the two genes, we quantified the expression of downstream genes in IL10 signaling or TGFB1 signaling. We observed that the examined genes in IL10 signaling were significantly repressed, especially IL5, which showed 5.4-fold decreased expression. Most genes were not altered in TGFB1 signaling, and the production of endogenous TGFB1 was significantly inhibited. These evidences collectively proved that the activation of IL0 and TGFB1 protected the host from antigen-induced asthma, possibly through IL10 signaling. This study shed some light on the modulations of IL10 and TGFB1, and related networks to asthma progression.
authors.affiliation: The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Street, Nanchang City, 330006, Jiangxi province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Street, Nanchang City, 330006, Jiangxi province, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Kang
authors.affiliation: The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Street, Nanchang City, 330006, Jiangxi province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Street, Nanchang City, 330006, Jiangxi province, China.
authors.forename: Chuanhui
authors.initials: C
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Street, Nanchang City, 330006, Jiangxi province, China.
authors.forename: Gen
authors.initials: G
authors.lastname: Hu
authors.affiliation: The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Street, Nanchang City, 330006, Jiangxi province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bai
authors.affiliation: The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Street, Nanchang City, 330006, Jiangxi province, China. zhangweiliuxin@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D010047:Ovalbumin / Q000633:toxicity; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: C556062:IL10 protein, mouse; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D010047:Ovalbumin
keywords: Asthma; IL10; Mouse model; TGFB1