Peptidase allergen Der p 1 initiates apoptosis of epithelial cells independently of tight junction proteolysis.

Abstract:

:Loss of epithelial cell polarity, which can arise following disruption of tight junctions (TJs), is a precursor to the care-fully orchestrated removal of moribund cells from epithelia in apoptosis. Ordinarily, this cycle of events has minimally disruptive effects on the function of the epithelial barrier, but some agents have been identified that induce apoptosis and promote epithelial leakiness. The allergen Der p 1 is a cysteine peptidase that cleaves TJ adhesion proteins and induces apoptosis in epithelial cells. This suggests the possibility that, at least for some inducers of apoptosis, these events might be causally linked. We report here that Der p 1 induces epithelial apoptosis before outright cell detachment and that apoptosis occurs within the same time span as increased paracellular permeability in polarized epithelial monolayers. Whilst TJ-deficient BEAS-2B cells were resistant to Der p 1-induced apoptosis, the cell line 1HAEo-, which was also TJ deficient, was sensitive to Der p 1, providing evidence against TJ proteolysis as a cause of apoptosis. To provide direct evidence, we propagated cells that normally express TJs in low calcium medium that prevented intercellular junction assembly. These cells retained full susceptibility to Der p 1, indicating that Der p 1-induced apoptosis is independent from TJ proteolysis.

journal_name

Mol Membr Biol

authors

Baker SF,Yin Y,Runswick SK,Stewart GA,Thompson PJ,Garrod DR,Robinson C

doi

10.1080/0968768021000061150

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

71-81

issue

1

eissn

0968-7688

issn

1464-5203

pii

8WYETNJHT7TJ7XRQ

journal_volume

20

pub_type

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