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Concurrent proinflammatory and apoptotic activity of a Helicobacter pylori protein (HP986) points to its role in chronic persistence

Alvi, Ayesha and Ansari, Suhail A. and Ehtesham, Nasreen Z. and Rizwan, Mohammed and Devi, Savita and Sechi, Leonardo Antonio and Qureshi, Insaf A. and Hasnain, Seyed E. and Ahmed, Niyaz (2011) Concurrent proinflammatory and apoptotic activity of a Helicobacter pylori protein (HP986) points to its role in chronic persistence. PLoS One, Vol. 6 (7), e22530. ISSN 1932-6203. Article.

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DOI: 10.1371/journal.pone.0022530

Abstract

Helicobacter pylori induces cytokine mediated changes in gastroduodenal pathophysiology, wherein, the activated macrophages at the sub-mucosal space play a central role in mounting innate immune response against the antigens. The bacterium gains niche through persistent inflammation and local immune-suppression causing peptic ulcer disease or chronic gastritis; the latter being a significant risk factor for the development of gastric adenocarcinoma. What favors persistence of H. pylori in the gastric niches is not clearly understood. We report detailed characterization of a functionally unknown gene (HP986), which was detected in patient isolates associated with peptic ulcer and gastric carcinoma. Expression and purification of recombinant HP986 (rHP986) revealed a novel, ~29 kDa protein in biologically active form which associates with significant levels of humoral immune responses in diseased individuals (p<0.001). Also, it induced significant levels of TNF-α and Interleukin-8 in cultured human macrophages concurrent to the translocation of nuclear transcription factor-κB (NF-κB). Further, the rHP986 induced apoptosis of cultured macrophages through a Fas mediated pathway. Dissection of the underlying signaling mechanism revealed that rHP986 induces both TNFR1 and Fas expression to lead to apoptosis. We further demonstrated interaction of HP986 with TNFR1 through computational and experimental approaches. Independent proinflammatory and apoptotic responses triggered by rHP986 as shown in this study point to its role, possibly as a survival strategy to gain niche through inflammation and to counter the activated macrophages to avoid clearance.

Item Type:Article
ID Code:6404
Status:Published
Refereed:Yes
Uncontrolled Keywords:Helicobacter pylori, gastro-duodenal diseases
Subjects:Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Public Library of Science
ISSN:1932-6203
Copyright Holders:© 2011 Alvi et al.
Deposited On:25 Aug 2011 10:59

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