Enteric Expression of the Integrin αvβ6 Is Essential for Nematode-Induced Mucosal Mast Cell Hyperplasia and Expression of the Granule Chymase, Mouse Mast Cell Protease-1

Pamela A. Knight, Steven H. Wright, Jeremy K. Brown, Xiaozhu Huang, Dean Sheppard, Hugh R.p. Miller

Research output: Contribution to journalArticlepeer-review

Abstract

The immunoregulatory cytokine transforming growth factor (TGF)-β1 is secreted as a biologically inactive complex with latency-associated peptide, which must be modified by local factors to expose the functionally active cytokine. The epithelial integrin αvβ6 mediates local activation of TGF-β1 in the lung and β6−/− mice exhibit exaggerated pulmonary inflammation, but their response to inflammatory stimuli in the gut has not been investigated. We found that both β6 and TGF-β1 are constitutively expressed in the jejunal epithelial compartment in uninfected mice and during infection with the intestinal nematode Nippostrongylus brasiliensis. We also present data showing that β6−/− mice are seriously compromised in their ability to mount a mucosal mast cell response after infection, and there is a significant reduction in the expression and systemic release of the granule chymase, mouse mast cell protease-1. Because in vitro expression of this chymase is regulated by TGF-β1, these data indicate that in the absence of αvβ6 epithelially expressed TGF-β1 may not be activated, with a consequent absence of expression of mouse mast cell protease-1 and down-regulation of the mucosal mast cell response.
Original languageEnglish
Pages (from-to)771-779
JournalAmerican Journal of Pathology
Volume161
Issue number3
DOIs
Publication statusPublished - 1 Sep 2002

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