Integrin β4 was downregulated on the airway epithelia of asthma patients

Abstract

The shedding of airway epithelial cells and loss of epithelial functional homeostasis are major pathological characteristics of asthma; however, the mechanism underlying these pathologies remains obscure. Our previous work showed that there were three variation sites in 5 0 flanking region of integrin b4 in asthma patients, which was correlated with decreased expression of integrin b4 in peripheral leukocytes. Integrin b4 is an important structural adhesion molecule on airway epithelia to keep the structural adhesion of epithelial cells. In this work, we further demonstrated that integrin b4 expression was downregulated in airway epithelia of asthma patients. To probe the relationship between imbalanced expression of integrin b4 and dysfunction of the airway epithelial cells in asthma, integrin b4 was silenced in human bronchial epithelium cells (16HBE14O) by integrin b4 small-interfering RNA lentivirus vector. Upon silencing of integrin b4, 16HBE14O cells showed reduced proliferation and wound repair. Most cells were shown to be arrested in G1 phase after integrin b4 silencing, and increased apoptosis was induced in the integrin b4-silenced cells. In summary, our results provided compelling evidence that integrin b4 was involved in the structural integrity and functional homeostasis of airway epithelial cells. It is likely that downregulation of integrin b4 on asthma airway epithelia contributes to the structural disruption and dysfunction of airway epithelial cells.

Analysis on the Relevance of Asthma Susceptibility with the Alteration of Integrin β 4 Expression

“…The downregulation of integrin β4 expression was verified by real-time PCR and western blot. Furthermore, our group has also demonstrated that integrin β4 was downregulated in airway epithelial cells of asthmatic patients[26].…”

“…The integrin β4 gene knock-out mice were shown to have cell cycle and adhesion defect[29]. As the first cell barrier to outer allergens, the airway epithelial cells showed a decreased wound repair and anti-oxidation ability after integrin β4 was downregulated[26], [30], [31]. Furthermore, downregulation of integrin β4 expression in airway epithelial cells could impair the antigen presentation ability of these cells, which further regulates airway inflammation reaction in allergic asthma[32].…”

Downregulation of Integrin β4 Decreases the Ability of Airway Epithelial Cells to Present Antigens

“…The effective ITGB4 siRNA and control siRNA were annealed and ligated into the new pGCSIL-PUR vector to create an ITGB4 siRNA expression vector and a control expression vector (Genechem, China, Shanghai) [14]. All plasmids were sequenced to confirm that they were correct.…”

“…Our previous work demonstrated that structural adhesion molecule integrin β4 (ITGB4) is downregulated in asthma airway epithelial cells. As the first cell barrier to outer allergens, the airway epithelial cells showed a decreased wound repair and anti-oxidation ability after ITGB4 was downregulated [14], [15]. ITGB4 is an important adhesion molecule that mediates the anchoring of airway epithelial cells to the basal membrane.…”

Role of bombesin receptor activated protein in the antigen presentation by human bronchial epithelial cells

“…Bronchial epithelial cells line the surface of airways, forming the first barrier to the external environment and play a critical role in the stabilization of airway microenvironment homeostasis. Increasing evidence indicates that bronchial epithelial cell lining is not merely a simple mechanic barrier that segregates the outside environment from the internal environment, but is also engaged in the regulation of local immune responses by producing cytokine and chemokines [Pichavant et al, 2003; Liu et al, 2010]. Moreover, bronchial epithelial cells express major histocompatibility complex (MHC) class I and class II molecules and co‐stimulatory molecules such as the B7 family and toll like receptors.…”