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Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock : Downstream Regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 Expression
Joint Authors
Sampaio, André L. F.
Wheatley, Carmen
Dalli, Jesmond
Perretti, Mauro
Brancaleone, Vincenzo
D'Acquisto, Fulvio
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-20, 20 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-05-28
Country of Publication
Egypt
No. of Pages
20
Main Subjects
Abstract EN
Background.
NOS/•NO inhibitors are potential therapeutics for sepsis, yet they increase clinical mortality.
However, there has been no in vivo investigation of the (in vitro) •NO scavenger, cobalamin’s (Cbl) endogenous effects on NOS/•NO/inflammatory mediators during the immune response to sepsis.
Methods.
We used quantitative polymerase chain reaction (qPCR), ELISA, Western blot, and NOS Griess assays, in a C57BL/6 mouse, acute endotoxaemia model.
Results.
During the immune response, pro-inflammatory phase, parenteral hydroxocobalamin (HOCbl) treatment partially inhibits hepatic, but not lung, iNOS mRNA and promotes lung eNOS mRNA, but attenuates the LPS hepatic rise in eNOS mRNA, whilst paradoxically promoting high iNOS/eNOS protein translation, but relatively moderate •NO production.
HOCbl/NOS/•NO regulation is reciprocally associated with lower 4 h expression of TNF-α, IL-1β, COX-2, and lower circulating TNF-α, but not IL-6.
In resolution, 24 h after LPS, HOCbl completely abrogates a major late mediator of sepsis mortality, high mobility group box 1 (HMGB1) mRNA, inhibits iNOS mRNA, and attenuates LPS-induced hepatic inhibition of eNOS mRNA, whilst showing increased, but still moderate, NOS activity, relative to LPS only.
experiments (LPS+D-Galactosamine) HOCbl afforded significant, dose-dependent protection in mice Conclusions.
HOCbl produces a complex, time- and organ-dependent, selective regulation of NOS/•NO during endotoxaemia, corollary regulation of downstream inflammatory mediators, and increased survival.
This merits clinical evaluation.
American Psychological Association (APA)
Sampaio, André L. F.& Dalli, Jesmond& Brancaleone, Vincenzo& D'Acquisto, Fulvio& Perretti, Mauro& Wheatley, Carmen. 2013. Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock : Downstream Regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 Expression. Mediators of Inflammation،Vol. 2013, no. 2013, pp.1-20.
https://search.emarefa.net/detail/BIM-495082
Modern Language Association (MLA)
Sampaio, André L. F.…[et al.]. Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock : Downstream Regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 Expression. Mediators of Inflammation No. 2013 (2013), pp.1-20.
https://search.emarefa.net/detail/BIM-495082
American Medical Association (AMA)
Sampaio, André L. F.& Dalli, Jesmond& Brancaleone, Vincenzo& D'Acquisto, Fulvio& Perretti, Mauro& Wheatley, Carmen. Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock : Downstream Regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 Expression. Mediators of Inflammation. 2013. Vol. 2013, no. 2013, pp.1-20.
https://search.emarefa.net/detail/BIM-495082
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-495082