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.
Asthma IL10 TGFB1 Mouse model
This research was funded by National Natural Science Foundation of China (30860105).
Al-Alawi M et al (2014) Transforming growth factor beta and severe asthma: a perfect storm. Respir Med 108:1409–1423CrossRefPubMedGoogle Scholar
Bentley AM et al (1996) Prednisolone treatment in asthma. Reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa. Am J Respir Crit Care Med 153:551–556CrossRefPubMedGoogle Scholar
Berkman N et al (1995) Inhibition of macrophage inflammatory protein-1 alpha expression by IL-10. Differential sensitivities in human blood monocytes and alveolar macrophages. J Immunol 155:4412–4418PubMedGoogle Scholar
Dekkers BG et al (2010) The integrin-blocking peptide RGDS inhibits airway smooth muscle remodeling in a guinea pig model of allergic asthma. Am J Respir Crit Care Med 181:556–565CrossRefPubMedGoogle Scholar
Grissell TV et al (2005) Interleukin-10 gene expression in acute virus-induced asthma. Am J Respir Crit Care Med 172:433–439CrossRefPubMedGoogle Scholar
Hinck AP (2012) Structural studies of the TGF-betas and their receptors—insights into evolution of the TGF-beta superfamily. FEBS Lett 586:1860–1870CrossRefPubMedGoogle Scholar
Hsu CY et al (2010) Synergistic therapeutic effects of combined adenovirus-mediated interleukin-10 and interleukin-12 gene therapy on airway inflammation in asthmatic mice. J Gene Med 12:11–21CrossRefPubMedGoogle Scholar
Kokturk N et al (2003) Expression of transforming growth factor beta1 in bronchial biopsies in asthma and COPD. J Asthma Off J Assoc Care Asthma 40:887–893CrossRefGoogle Scholar
Makinde T et al (2007) The regulatory role of TGF-beta in airway remodeling in asthma. Immunol Cell Biol 85:348–356CrossRefPubMedGoogle Scholar
Michaeloudes C et al (2011) TGF-beta regulates Nox4, MnSOD and catalase expression, and IL-6 release in airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 300:L295–L304CrossRefPubMedGoogle Scholar