Journal article

TNF and granulocyte macrophage-colony stimulating factor interdependence mediates inflammation via CCL17

Andrew D Cook, Ming-Chin Lee, Reem Saleh, Hsu-Wei Khiew, Anne D Christensen, Adrian Achuthan, Andrew J Fleetwood, Derek C Lacey, Julia E Smith, Irmgard Foerster, John A Hamilton

JCI INSIGHT | AMER SOC CLINICAL INVESTIGATION INC | Published : 2018

Abstract

TNF and granulocyte macrophage-colony stimulating factor (GM-CSF) have proinflammatory activity and both contribute, for example, to rheumatoid arthritis pathogenesis. We previously identified a new GM-CSF→JMJD3 demethylase→interferon regulatory factor 4 (IRF4)→CCL17 pathway that is active in monocytes/macrophages in vitro and important for inflammatory pain, as well as for arthritic pain and disease. Here we provide evidence for a nexus between TNF and this pathway, and for TNF and GM-CSF interdependency. We report that the initiation of zymosan-induced inflammatory pain and zymosan-induced arthritic pain and disease are TNF dependent. Once arthritic pain and disease are established, blocka..

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Grants

Awarded by Deutsche Forschungsgemeinschaft (DFG)



Funding Acknowledgements

A. Achuthan and J.A. Hamilton were supported in part by a grant from GSK. A.D. Cook and J.A. Hamilton were supported by a grant (1043147), and J.A. Hamilton by a Senior Principal Research Fellowship from the National Health and Medical Research Council of Australia. A.D. Christensen was supported by a Postdoc Fellowship from Novo Nordisk A/S, Denmark. I. Forster was supported by the Deutsche Forschungsgemeinschaft IRTG 2168 (DFG).