An altered REDOX environment, assisted by over-expression of fetal hemoglobins, protects from inflammatory colitis and reduces inflammatory cytokine expression.

Details

Serval ID
serval:BIB_D2FDD04698DF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
An altered REDOX environment, assisted by over-expression of fetal hemoglobins, protects from inflammatory colitis and reduces inflammatory cytokine expression.
Journal
International immunopharmacology
Author(s)
Gorczynski R.M., Alexander C., Brandenburg K., Chen Z., Heini A., Neumann D., Mach J.P., Rietschel E.T., Tersikh A., Ulmer A.J., Yu K., Zahringer U., Khatri I.
ISSN
1878-1705 (Electronic)
ISSN-L
1567-5769
Publication state
Published
Issued date
09/2017
Peer-reviewed
Oui
Volume
50
Pages
69-76
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
Animals, Colitis/chemically induced, Colitis/drug therapy, Colitis/metabolism, Cytokines/metabolism, Dextran Sulfate, Disease Models, Animal, Female, Fetal Proteins/genetics, Fetal Proteins/metabolism, Furaldehyde/analogs & derivatives, Furaldehyde/therapeutic use, Hemoglobins/genetics, Hemoglobins/metabolism, Humans, Hydroxyurea/therapeutic use, Inflammation Mediators/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Oxidation-Reduction, Sirolimus/therapeutic use, DSS-colitis, Fetal hemoglobins, Inflammatory cytokines, REDOX environment
Pubmed
Web of science
Create date
06/07/2017 17:33
Last modification date
20/08/2019 15:53
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