Titre
An altered REDOX environment, assisted by over-expression of fetal hemoglobins, protects from inflammatory colitis and reduces inflammatory cytokine expression.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Gorczynski, R.M.
Auteure/Auteur
Alexander, C.
Auteure/Auteur
Brandenburg, K.
Auteure/Auteur
Chen, Z.
Auteure/Auteur
Heini, A.
Auteure/Auteur
Neumann, D.
Auteure/Auteur
Mach, J.P.
Auteure/Auteur
Rietschel, E.T.
Auteure/Auteur
Tersikh, A.
Auteure/Auteur
Ulmer, A.J.
Auteure/Auteur
Yu, K.
Auteure/Auteur
Zahringer, U.
Auteure/Auteur
Khatri, I.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1878-1705
Statut éditorial
Publié
Date de publication
2017-09
Volume
50
Première page
69
Dernière page/numéro d’article
76
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
C5BL/6 female mice receiving dextran sodium sulfate in their drinking water develop an acute inflammatory colitis within 7d, with weight loss, histopathologic signs of inflammation, and colonic expression of inflammatory cytokines. In previous studies we have reported that increased inflammatory cytokine expression in aged mice can be attenuated by oral gavage of a crude fetal extract containing glutathione (GSH), MPLA and fetal hemoglobin, or more specifically by injection of a combination of these purified reagents. We speculated that this combination led to an altered tissue redox environment in which the immune response developed, thus regulating inflammation. Accordingly, we used wild-type (WT) C57BL/6 mice, or mice lacking either murine beta Hemoglobin major (Hgbβ <sub>ma</sub> KO) or minor (Hgbβ <sub>mi</sub> KO) as recipients of DSS in their drinking water, and followed development of colitis both clinically and by inflammatory cytokine production, before/after oral treatment of mice with a crude fetal liver extract. Mice lacking an intact fetal hemoglobin chain (Hgbβ <sub>mi</sub> KO) developed severe colitis, with enhanced colonic expression of inflammatory cytokines, which could not be rescued by extract, unlike WT and Hgbβ <sub>ma</sub> KO animals. Moreover, disease in both WT and Hgbβ <sub>ma</sub> KO animals could also be attenuated by exposure to 5-hydroxymethyl furfural (5HMF), hydroxyurea or rapamycin. The former has been used as an alternative means of stabilizing the conformation of adult hemoglobin in a manner which mimicks the oxygen-affinity of fetal hemoglobin, while we show that both hydroxyurea and rapamycin augment expression of murine fetal hemoglobin chains. Our data suggests there may be a clinical value in exploring agents which alter local REDOX environments as an adjunctive treatment for colitis and attenuating inflammatory cytokine production.
Sujets
PID Serval
serval:BIB_D2FDD04698DF
PMID
Date de création
2017-07-06T16:33:30.560Z
Date de création dans IRIS
2025-05-21T01:02:45Z