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Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation

Keyel, PA and Romero, M and Wu, W and Kwak, DH and Zhu, Q and Liu, X and Salter, RD (2014) Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation. PLoS ONE, 9 (8).

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Abstract

Regulation of inflammation is necessary to balance sufficient pathogen clearance with excessive tissue damage. Central to regulating inflammation is the switch from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are well-positioned to initiate this switch, and as such are the target of multiple therapeutics. One such potential therapeutic is methylthioadenosine (MTA), which inhibits TNFα production following LPS stimulation. We found that MTA could block TNFα production by multiple TLR ligands. Further, it prevented surface expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that the mechanism of this action by MTA is signaling through adenosine A2 receptors. A2 receptors and TLR receptors synergized to promote an anti-inflammatory phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1β production and processing was not affected by MTA exposure. Taken together, these data demonstrate that MTA reprograms TLR activation pathways via adenosine receptors to promote resolution of inflammation. © 2014 Keyel et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Keyel, PA
Romero, M
Wu, W
Kwak, DH
Zhu, Q
Liu, Xxinyuliu@pitt.eduXINYULIU
Salter, RD
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorArendt, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 12 August 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0104210
Schools and Programs: School of Medicine > Immunology
Refereed: Yes
Date Deposited: 23 Sep 2014 15:01
Last Modified: 13 Oct 2017 21:58
URI: http://d-scholarship.pitt.edu/id/eprint/22994

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