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Resolution of Sterile Inflammation: Role for Vitamin C

Introduction. Macrophage reprogramming is vital for resolution of acute inflammation. Parenteral vitamin C (VitC) attenuates proinflammatory states in murine and human sepsis. However information about the mechanism by which VitC regulates resolution of inflammation is limited. Methods. To examine w...

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Autores principales: Mohammed, Bassem M., Fisher, Bernard J., Huynh, Quoc K., Wijesinghe, Dayanjan S., Chalfant, Charles E., Brophy, Donald F., Fowler III, Alpha A., Natarajan, Ramesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175383/
https://www.ncbi.nlm.nih.gov/pubmed/25294953
http://dx.doi.org/10.1155/2014/173403
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author Mohammed, Bassem M.
Fisher, Bernard J.
Huynh, Quoc K.
Wijesinghe, Dayanjan S.
Chalfant, Charles E.
Brophy, Donald F.
Fowler III, Alpha A.
Natarajan, Ramesh
author_facet Mohammed, Bassem M.
Fisher, Bernard J.
Huynh, Quoc K.
Wijesinghe, Dayanjan S.
Chalfant, Charles E.
Brophy, Donald F.
Fowler III, Alpha A.
Natarajan, Ramesh
author_sort Mohammed, Bassem M.
collection PubMed
description Introduction. Macrophage reprogramming is vital for resolution of acute inflammation. Parenteral vitamin C (VitC) attenuates proinflammatory states in murine and human sepsis. However information about the mechanism by which VitC regulates resolution of inflammation is limited. Methods. To examine whether physiological levels of VitC modulate resolution of inflammation, we used transgenic mice lacking L-gulono-γ-lactone oxidase. VitC sufficient/deficient mice were subjected to a thioglycollate-elicited peritonitis model of sterile inflammation. Some VitC deficient mice received daily parenteral VitC (200 mg/kg) for 3 or 5 days following thioglycollate infusion. Peritoneal macrophages harvested on day 3 or day 5 were examined for intracellular VitC levels, pro- and anti-inflammatory protein and lipid mediators, mitochondrial function, and response to lipopolysaccharide (LPS). The THP-1 cell line was used to determine the modulatory activities of VitC in activated human macrophages. Results. VitC deficiency significantly delayed resolution of inflammation and generated an exaggerated proinflammatory response to in vitro LPS stimulation. VitC sufficiency and in vivo VitC supplementation restored macrophage phenotype and function in VitC deficient mice. VitC loading of THP-1 macrophages attenuated LPS-induced proinflammatory responses. Conclusion. VitC sufficiency favorably modulates macrophage function. In vivo or in vitro VitC supplementation restores macrophage phenotype and function leading to timely resolution of inflammation.
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spelling pubmed-41753832014-10-07 Resolution of Sterile Inflammation: Role for Vitamin C Mohammed, Bassem M. Fisher, Bernard J. Huynh, Quoc K. Wijesinghe, Dayanjan S. Chalfant, Charles E. Brophy, Donald F. Fowler III, Alpha A. Natarajan, Ramesh Mediators Inflamm Research Article Introduction. Macrophage reprogramming is vital for resolution of acute inflammation. Parenteral vitamin C (VitC) attenuates proinflammatory states in murine and human sepsis. However information about the mechanism by which VitC regulates resolution of inflammation is limited. Methods. To examine whether physiological levels of VitC modulate resolution of inflammation, we used transgenic mice lacking L-gulono-γ-lactone oxidase. VitC sufficient/deficient mice were subjected to a thioglycollate-elicited peritonitis model of sterile inflammation. Some VitC deficient mice received daily parenteral VitC (200 mg/kg) for 3 or 5 days following thioglycollate infusion. Peritoneal macrophages harvested on day 3 or day 5 were examined for intracellular VitC levels, pro- and anti-inflammatory protein and lipid mediators, mitochondrial function, and response to lipopolysaccharide (LPS). The THP-1 cell line was used to determine the modulatory activities of VitC in activated human macrophages. Results. VitC deficiency significantly delayed resolution of inflammation and generated an exaggerated proinflammatory response to in vitro LPS stimulation. VitC sufficiency and in vivo VitC supplementation restored macrophage phenotype and function in VitC deficient mice. VitC loading of THP-1 macrophages attenuated LPS-induced proinflammatory responses. Conclusion. VitC sufficiency favorably modulates macrophage function. In vivo or in vitro VitC supplementation restores macrophage phenotype and function leading to timely resolution of inflammation. Hindawi Publishing Corporation 2014 2014-09-09 /pmc/articles/PMC4175383/ /pubmed/25294953 http://dx.doi.org/10.1155/2014/173403 Text en Copyright © 2014 Bassem M. Mohammed et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mohammed, Bassem M.
Fisher, Bernard J.
Huynh, Quoc K.
Wijesinghe, Dayanjan S.
Chalfant, Charles E.
Brophy, Donald F.
Fowler III, Alpha A.
Natarajan, Ramesh
Resolution of Sterile Inflammation: Role for Vitamin C
title Resolution of Sterile Inflammation: Role for Vitamin C
title_full Resolution of Sterile Inflammation: Role for Vitamin C
title_fullStr Resolution of Sterile Inflammation: Role for Vitamin C
title_full_unstemmed Resolution of Sterile Inflammation: Role for Vitamin C
title_short Resolution of Sterile Inflammation: Role for Vitamin C
title_sort resolution of sterile inflammation: role for vitamin c
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175383/
https://www.ncbi.nlm.nih.gov/pubmed/25294953
http://dx.doi.org/10.1155/2014/173403
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