Anthrax infection inhibits the AKT signaling involved in the E-cadherin-mediated adhesion of lung epithelial cells

Popova, Taissia; Espina, Virginia; Bailey, Charles; Liotta, Lance; Petricoin, Emanuel; Popov, Serguei

doi:10.1111/j.1574-695x.2009.00558.x

Title: Anthrax infection inhibits the AKT signaling involved in the E-cadherin-mediated adhesion of lung epithelial cells

Journal Article · Wed Jul 01 00:00:00 EDT 2009 · FEMS Immunology & Medical Microbiology

DOI:https://doi.org/10.1111/j.1574-695x.2009.00558.x· OSTI ID:1625901

Popova, Taissia ^[1]; Espina, Virginia ^[2]; Bailey, Charles ^[1]; Liotta, Lance ^[2]; Petricoin, Emanuel ^[2]; Popov, Serguei ^[1]

George Mason Univ., Fairfax, VA (United States). National Center for Biodefense and Infectious Diseases
George Mason Univ., Fairfax, VA (United States). Center for Applied Proteomics and Molecular Medicine

The effect of anthrax infection on phosphoprotein signaling was studied in human small airway lung epithelial cells exposed to B. anthracis spores of the plasmidless dSterne strain in comparison with the Sterne strain containing the toxigenic plasmid (pXO1). The differential regulation of phosphorylation was found in the mitogen-activated protein kinase cascade (ERK, p38, and P90RSK), the PI3K cascade (AKT, GSK-3α/β), and downstream in the case of the proapoptotic BAD and the transcription factor STAT3. Both strains stimulate phosphorylation of CREB and inhibit phosphorylation of 4E-BP1 required for activation of cap-dependent translation. Downregulation of the survival AKT phosphorylation by the Sterne strain inhibits the process of Ca²⁺-dependent homophilic interaction of E-cadherin (EC) upon formation or repair of cell–cell contacts. Both lethal and edema toxins produced by the Sterne strain inhibit the AKT phosphorylation induced during the EC-mediated signaling. Activity of ERK1/2 and p38 inhibitors indicates that inhibition of AKT phosphorylation takes place through the ERK1/2-PI3K crosstalk. In Sterne spore-challenged mice, a specific inhibitor of PI3K/AKT, wortmannin, accelerates the lethal outcome, and reduction of AKT phosphorylation in the circulating blood cells coincides with the death of animals. We conclude that the PI3K/AKT pathway controlling the integrity of epithelium plays an important survival role in anthrax infection.

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Research Organization:: George Mason Univ., Fairfax, VA (United States)

Sponsoring Organization:: USDOE; USDOD

Grant/Contract Number:: FC52-04NA25455; DAMD17-03-C-0122

OSTI ID:: 1625901

Journal Information:: FEMS Immunology & Medical Microbiology, Vol. 56, Issue 2; ISSN 0928-8244

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
59 BASIC BIOLOGICAL SCIENCES
immunology
infectious diseases
microbiology
reverse-phase microarray
cell signaling
epithelial cells
AKT
cell–cell adherence

Title: Anthrax infection inhibits the AKT signaling involved in the E-cadherin-mediated adhesion of lung epithelial cells

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