Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation

Peter A. Keyel, Matthew Romero, Wenbo Wu, Daniel H. Kwak, Qin Zhu, Xinyu Liu, Russell D. Salter

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish
Article numbere104210
JournalPloS one
Issue number8
StatePublished - Aug 12 2014


Dive into the research topics of 'Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation'. Together they form a unique fingerprint.

Cite this