A Research Of Wnt/β-catenin Signaling In Alveolar Epithelial Cells Negative Feedback Regulating The Activity Of BCG Induced TLR Signal Mechanism

Mycobacterium tuberculosis (Mycobacterium Tuberculosis, Mtb) is a typical intracellular parasite, alveolar macrophages as immunomodulators and effector cells in the course of infection by phagocytosis, antigen presentation and cytokine secretion of various functions to regulate inflammatory response and immune response. Recent studies have found that the type Ⅱ alveolar epithelial cell (Alveolar epithelial type Ⅱ cells, AECⅡ) and macrophages as tuberculosis pathogen is also the first infected target cells; AEC Ⅱ in addition to the normal process of cell renewal and repair damage in the lungs proliferation and differentiation of alveolar type Ⅰ and type Ⅱ epithelial cells and the synthesis and secretion of pulmonary surfactant, maintaining alveolar fluid balance inside and outside, still in the lungs against exogenous microbial infection plays an important role in immune regulation, this role allows AEC Ⅱ cells become one of the hot research. In the AEC Ⅱ cells should exogenous microorganisms (such as Mycobacterium tuberculosis) infection by a variety of complex regulatory signaling network, specific regulatory mechanisms still being studied and explored. The Wnt signaling pathway as a key organization involved in developmental processes such as cell migration and specialization in the process of Mycobacterium tuberculosis infection in the lungs, and it is in the AEC Ⅱ cells of innate immunity also play an important regulatory role, has yet to see the report. Therefore, this study type Ⅱ alveolar epithelial cell line A549cells as a model to analyze changes in their before and after Mycobacterium bovis BCG (BCG) and lipopolysaccharide (LPS) stimulation of Wnt/β-catenin signaling pathway and inflammatory factors related signals and Toll-like recepters signals through interactions between and, in order to explore the Wnt signaling pathway in the organism Mycobacterium tuberculosis infection in AEC II cells in the immune regulatory role. By experiment, the following results obtained:1. A549cells in the BCG and LPS stimulation, and by up-regulating the expression of Axin GSK3β to inhibit the β-catenin, LEF-1and TCF4expression, thereby inhibiting the activity of the Wnt/β-catenin signaling pathway,2. A549cells after BCG and LPS stimulation, Toll signaling pathway MyD88, TRAF6and NF-kb increase occurs, resulting in inflammatory cytokines IL-6, IL-2, IL-8, TNF-a secretion; while in A549cells over-expression of P-catenin or the addition of Wnt3a conditioned medium, the inflammatory cytokines and factors reduced TLR signaling pathway, suggesting that the alveolar epithelial cells, Wnt signal BCG and LPS stimulation inhibited inflammation, thereby protecting cells from excessive inflammatory response to injury;3. In A549cells overexpressing TLR signaling pathway critical factor MyD88, Wnt signaling pathway in the β-catenin, the expression of FZD-1and cyclinDl occurred down, suggesting that TLR signaling pathway Wnt/β-catenin signaling pathway activation inhibited. In summary, in the alveolar epithelial cells of Mycobacterium tuberculosis and to maintain the balance of LPS stimulation of inflammation negative feedback regulation by Wnt/β-catenin signaling pathway and between the TLR signaling pathway.