ATP-dependent activation of an inflammasome in primary gingival epithelial cells infected by Porphyromonas gingivalis

ORCiD

David M. Ojcius: 0000-0003-1461-4495

Department

Biomedical Sciences

Document Type

Article

Publication Title

Cellular Microbiology

ISSN

1462-5814

Volume

12

Issue

2

DOI

10.1111/j.1462-5822.2009.01390.x

First Page

188

Last Page

198

Publication Date

2-1-2010

Abstract

Production of IL-1 beta typically requires two-separate signals. The first signal, from a pathogen-associated molecular pattern, promotes intracellular production of immature cytokine. The second signal, derived from a danger signal such as extracellular ATP, results in assembly of an inflammasome, activation of caspase-1 and secretion of mature cytokine. The inflammasome component, Nalp3, plays a non-redundant role in caspase-1 activation in response to ATP binding to P2X(7) in macrophages. Gingival epithelial cells (GECs) are an important component of the innate-immune response to periodontal bacteria. We had shown that GECs express a functional P2X(7) receptor, but the ability of GECs to secrete IL-1 beta during infection remained unknown. We find that GECs express a functional Nalp3 inflammasome. Treatment of GECs with LPS or infection with the periodontal pathogen, Porphyromonas gingivalis, induced expression of the il-1 beta gene and intracellular accumulation of IL-1 beta protein. However, IL-1 beta was not secreted unless LPS-treated or infected cells were subsequently stimulated with ATP. Conversely, caspase-1 is activated in GECs following ATP treatment but not P. gingivalis infection. Furthermore, depletion of Nalp3 by siRNA abrogated the ability of ATP to induce IL-1 beta secretion in infected cells. The Nalp3 inflammasome is therefore likely to be an important mediator of the inflammatory response in gingival epithelium.

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