Integrin v8-Mediated Activation of Transforming Growth Factor- Inhibits Human Airway Epithelial Proliferation in Intact Bronchial Tissue

Transforming growth factor (TGF)- is a potent mul-tifunctional cytokine that is an essential regulator of epithelial proliferation. Because TGF- is expressed almost entirely in a latent state in vivo, a major source of regulation of TGF- function is its activation. A subset of integrins, v8 and v6, which are ex-pressed in the human airway, has recently been shown to activate latent TGF- in vitro, suggesting a regulatory role for integrins in TGF- function in vivo. Here we have developed a novel, biologically relevant experimental model of human airway epithelium us-ing intact human bronchial tissue. We have used this model to determine the function of integrin-mediated activation of TGF- in the airway. In human bronchial fragments cultured in vitro, authentic epithelial-stro