Anti-oxidant inhibition of hyaluronan fragment-induced inflammatory gene expression

Michael Eberlein; Kara A Scheibner; Katharine E Black; Samuel L Collins; Yee Chan-Li; Jonathan D Powell; Maureen R Horton

doi:10.1186/1476-9255-5-20

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Anti-oxidant inhibition of hyaluronan fragment-induced inflammatory gene expression

Journal article

Open access

Peer reviewed

Anti-oxidant inhibition of hyaluronan fragment-induced inflammatory gene expression

Michael Eberlein, Kara A Scheibner, Katharine E Black, Samuel L Collins, Yee Chan-Li, Jonathan D Powell and Maureen R Horton

Journal of inflammation (London, England), Vol.5(1), pp.20-20

2008

DOI: 10.1186/1476-9255-5-20

PMCID: PMC2627834

PMID: 18986521

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Abstract

Background: The balance between reactive oxygen species (ROS) and endogenous anti-oxidants is important in maintaining healthy tissues. Excessive ROS states occur in diseases such as ARDS and Idiopathic Pulmonary Fibrosis. Redox imbalance breaks down the extracellular matrix component hyaluronan (HA) into fragments that activate innate immune responses and perpetuate tissue injury. HA fragments, via a TLR and NF-kappaB pathway, induce inflammatory gene expression in macrophages and epithelial cells. NAC and DMSO are potent anti-oxidants which may help balance excess ROS states. Methods: We evaluated the effect of H2O2, NAC and DMSO on HA fragment induced inflammatory gene expression in alveolar macrophages and epithelial cells. Results: NAC and DMSO inhibit HA fragment-induced expression of TNF-alpha and KC protein in alveolar and peritoneal macrophages. NAC and DMSO also show a dose dependent inhibition of IP-10 protein expression, but not IL-8 protein, in alveolar epithelial cells. In addition, H2O2 synergizes with HA fragments to induce inflammatory genes, which are inhibited by NAC. Mechanistically, NAC and DMSO inhibit HA induced gene expression by inhibiting NF-kappaB activation, but NAC had no influence on HA-fragment-AP-1 mediated gene expression. Conclusion: ROS play a central role in a pathophysiologic "vicious cycle" of inflammation: tissue injury generates ROS, which fragment the extracellular matrix HA, which in turn synergize with ROS to activate the innate immune system and further promote ROS, HA fragment generation, inflammation, tissue injury and ultimately fibrosis. The anti-oxidants NAC and DMSO, by inhibiting the H

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Title: Subtitle: Anti-oxidant inhibition of hyaluronan fragment-induced inflammatory gene expression
Creators: Michael Eberlein - Department of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA
Kara A Scheibner - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Katharine E Black - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Samuel L Collins - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Yee Chan-Li - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Jonathan D Powell - Department of Oncology, Johns Hopkins University School of Medicine, 1830 E. Monument street, 5
Maureen R Horton - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Resource Type: Journal article
Publication Details: Journal of inflammation (London, England), Vol.5(1), pp.20-20
DOI: 10.1186/1476-9255-5-20
PMID: 18986521
PMCID: PMC2627834
NLM abbreviation: J Inflamm (Lond)
ISSN: 1476-9255
eISSN: 1476-9255
Publisher: BioMed Central
Language: English
Date published: 2008
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984094712102771

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