Blockade of the JNK Signalling as a Rational Therapeutic Approach to Modulate the Early and Late Steps of the Inflammatory Cascade in Polymicrobial Sepsis. (22nd March 2015)

• Record Type: Journal Article
• Authors: Pizzino, Gabriele; Bitto, Alessandra; Pallio, Giovanni; Irrera, Natasha; Galfo, Federica; Interdonato, Monica; Mecchio, Anna; De Luca, Filippo; Minutoli, Letteria; Squadrito, Francesco; Altavilla, Domenica
• Other Names: Lira Fábio Santos Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2015(2015)
• Publication Date: 2015-03-22
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2015/591572
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : Cecal ligation and puncture (CLP) is an experimental polymicrobial sepsis induced systemic inflammation that leads to acute organ failure. Aim of our study was to evaluate the effects of SP600125, a specific c-Jun NH2 -terminal kinase (JNK) inhibitor, to modulate the early and late steps of the inflammatory cascade in a murine model of CLP-induced sepsis. CB57BL/6J mice were subjected to CLP or sham operation. Animals were randomized to receive either SP600125 (15 mg/kg) or its vehicle intraperitoneally 1 hour after surgery and repeat treatment every 24 hours. To evaluate survival, a group of animals was monitored every 24 hours for 120 hours. Two other animals were sacrificed 4 or 18 hours after surgical procedures; lung and liver samples were collected for biomolecular and histopathologic analysis. The expression of p-JNK, p-ERK, TNF- α, HMGB-1, NF- κ B, Ras, Rho, Caspase 3, Bcl-2, and Bax was evaluated in lung and liver samples; SP600125 improved survival, reduced CLP induced activation of JNK, NF- κ B, TNF- α, and HMGB-1, inhibited proapoptotic pathway, preserved Bcl-2 expression, and reduced histologic damage in both lung and liver of septic mice. SP600125 protects against CLP induced sepsis by blocking JNK signalling; therefore, it can be considered a therapeutic approach in human sepsis.