Toll-like receptor-3-induced mitochondrial dysfunction in cultured human hepatocytes

Djafarzadeh, Siamak; Vuda, Madhusudanarao; Takala, Jukka; Ochs, Matthias; Jakob, Stephan M (2011). Toll-like receptor-3-induced mitochondrial dysfunction in cultured human hepatocytes. Mitochondrion, 11(1), pp. 83-8. Amsterdam: Elsevier 10.1016/j.mito.2010.07.010

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Several studies have shown the presence of liver mitochondrial dysfunction during sepsis. TLR3 recognizes viral double-stranded RNA and host endogenous cellular mRNA released from damaged cells. TLR3 ligand amplifies the systemic hyperinflammatory response observed during sepsis and in sepsis RNA escaping from damaged tissues/cells may serve as an endogenous ligand for TLR3 thereby modulating immune responses. This study addressed the hypothesis that TLR3 might regulate mitochondrial function in cultured human hepatocytes. HepG2 cells were exposed to TLR-3 ligand (dsRNA--polyinosine-polycytidylic acid; Poly I:C) and mitochondrial respiration was measured. Poly I:C induced a reduction in maximal mitochondrial respiration of human hepatocytes which was prevented partially by preincubation with cyclosporine A (a mitochondrial permeability transition pore-opening inhibitor). Poly-I:C induced activation of NF-κB, and the mitochondrial dysfunction was accompanied by caspase-8 but not caspase-3 activation and by no major alterations in cellular or mitochondrial ultrastructure.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care

UniBE Contributor:

Djafarzadeh, Siamak; Vuda, Madhusudanarao; Takala, Jukka and Jakob, Stephan

ISSN:

1567-7249

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:09

Last Modified:

06 Dec 2013 13:20

Publisher DOI:

10.1016/j.mito.2010.07.010

PubMed ID:

20691286

Web of Science ID:

000286450300012

URI:

https://boris.unibe.ch/id/eprint/968 (FactScience: 201578)

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