Inactivation of the integrin beta 6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin.

Lung Biology Center, University of California, San Francisco 94143, USA.
The Journal of Cell Biology (Impact Factor: 9.69). 06/1996; 133(4):921-8.
Source: PubMed

ABSTRACT The integrin alpha v beta 6 is only expressed in epithelial cells. In healthy adult epithelia, this receptor is barely detectable, but expression is rapidly induced following epithelial injury. Mice homozygous for a null mutation in the gene encoding the beta 6 subunit had juvenile baldness associated with infiltration of macrophages into the skin, and accumulated activated lymphocytes around conducting airways in the lungs. Beta 6-/- mice also demonstrated airway hyperresponsiveness to acetylcholine, a hallmark feature of asthma. These results suggest that the epithelial integrin alpha v beta 6 participates in the modulation of epithelial inflammation. Genetic or acquired alterations in this integrin could thus contribute to the development of inflammatory diseases of epithelial organs, such as the lungs and skin.

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Available from: Darrell Cass, Jul 14, 2015
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    • "A great number of studies have established that integrin binding is the main prerequisite for latent TGF-β1 activation, in particular in conditions of inflammation and fibrosis [110]. Knocking out integrin subunits that activate TGF-β1, including β6 [113], αv [114], and β8 [115], and mutation of the integrin binding site in LAP [116] all produce defects that are similar to the phenotype of the TGF-β1 knockout mouse [103]. Seminal work of Sheppard and coworkers have shown that β6 integrin was unable to active latent TGF-β1 without a functional cytoplasmic tail that intracellularly links to the actin cytoskeleton [117]. "
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    • "Interestingly, although mice lacking the TGF␤-activating integrin ␣v␤8 on immune cells develop autoimmunity, this is not as severe as mice that lack global function of integrins ␣v␤6 and ␣v␤8 (Aluwihare et al. 2009). Global integrin ␣v␤6−/− mice develop only mild inflammation of the lung and skin (Huang et al. 1996). "
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    • "We previously demonstrated that the epithelial-restricted integrin α v β 6 activates TGF-β and that Itgb6 −/− mice exhibit a phenotype mildly similar to Tgfb1 −/− mice [1] [14]. These mice are also dramatically protected in models of diseases that are mediated by TGF-β, supporting a role for α v β 6 in regulating TGF-β bioactivity in vivo [1] [4] [5] [9] [14]. Because of the importance of α v β 6 -mediated TGF-β activation in the pathogenesis of various disease states, we wanted to determine the molecular signals and mechanisms that regulate activation of this pathway. "
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