R Sordi is supported by the program Science without Borders, CAPES Foundation,
Ministry of Education of Brazil, Brasilia/DF, Brazil; NSA Patel is, in part, supported by the Bart’s and The LondonCharity (753/1722). The research leading
to these results has received funding from the People Programme (Marie
Curie Actions) of the European Union′s Seventh Framework Programme
(FP7/2007-2013) under REA grant agreement n° 608765, from the William Harvey
Research Foundation and University of Turin (Ricerca Locale ex-60%). This
work contributes to the Organ Protection
research theme of the Barts Centre
for Trauma Sciences, supported by the
Barts and The London Charity (Award
753/1722) and forms part of the research
themes contributing to the translational
research portfolio of Barts and the London
Cardiovascular Biomedical Research
Unit, which is supported and funded by
the National Institute of Health Researc

Brohi, K

Chiazza, F

Collino, M

Johnson, FL

Patel, NSA

Sordi, R

Thiemermann, C

Molecular Medicine

PubMed

Queen Mary Research Online

Inhibition of I kappa B Kinase Attenuates the Organ Injury and Dysfunction Associated with Hemorrhagic Shock

Regina Sordi

Fausto Chiazza

Florence L. Johnson

Nimesh S. A. Patel

Karim Brohi

Massimo Collino

Christoph Thiemermann

Crossref

Inhibition of IκB Kinase Attenuates the Organ Injury and Dysfunction Associated with Hemorrhagic Shock

Nuclear factor-kappa B (NF-κB) activation is widely implicated in multiple organ failure (MOF); however, a direct inhibitor of IκB kinase (IKK), which plays a pivotal role in the activation of NF-κB, has not been investigated in shock. Thus, the aim of the present work was to investigate the effects of an IKK inhibitor on the MOF associated with hemorrhagic shock (HS). Therefore, rats were subjected to HS and were resuscitated with the shed blood. Rats were treated with the inhibitor of IKK or vehicle at resuscitation. Four hours later, blood and organs were assessed for organ injury and signaling events involved in the activation of NF-κB. Additionally, survival following serum deprivation was assessed in HK-2 cells treated with the inhibitor of IKK. HS resulted in renal dysfunction, lung, liver and muscular injury, and increases in serum inflammatory cytokines. Kidney and liver tissue from HS rats revealed increases in phosphorylation of IKKαβ and IκBα, nuclear translocation of NF-κB and expression of inducible isoform of nitric oxide synthase (iNOS). IKK16 treatment upon resuscitation attenuated NF-κB activation and activated the Akt survival pathway, leading to a significant attenuation of all of the above parameters. Furthermore, IKK16 exhibited cytoprotective effects in human kidney cells. In conclusion, the inhibitor of IKK complex attenuated the MOF associated with HS. This effect may be due to the inhibition of the NF-κB pathway and activation of the survival kinase Akt. Thus, the inhibition of the IKK complex might be an effective strategy for the prevention of MOF associated with HS

Sordi, Regina

CHIAZZA, FAUSTO

Johnson, Florence L.

Patel, Nimesh S. A.

Brohi, Karim

COLLINO, Massimo

Thiemermann, Christoph

Archivio Istituzionale della Ricerca- Università del Piemonte Orientale

Inhibition of IκB kinase attenuates the organ injury and dysfunction associated with hemorrhagic shock

Chiazza, Fausto

Collino, Massimo

Institutional Research Information System University of Turin

English

https://iris.unito.it/bitstream/2318/1563242/1/2015%20Molecular%20Medicine%20IKK%20HS.pdf

Inhibition of I kappa B Kinase Attenuates the Organ Injury and Dysfunction Associated with Hemorrhagic Shock

Abstract

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Queen Mary Research Online

Crossref

Archivio Istituzionale della Ricerca- Università del Piemonte Orientale

Institutional Research Information System University of Turin