A new monocyte/macrophage-mediated pathway in inflammation and associated pain

Granulocyte macrophage-colony stimulating factor (GM-CSF) has been implicated in the pathogenesis of a number of inflammatory diseases and in osteoarthritis (OA). We have identified a new GM-CSF→Jmjd3→interferon regulatory factor 4 (IRF4)→ chemokine (c-c motif) ligand 17 (CCL17) pathway in moncocytes/macrophages, which is important for the development of inflammatory arthritis pain and disease. Tumour necrosis factor (TNF) can be linked with this pathway. We also found that the GM-CSF→Jmjd3→IRF4→CCL17 pathway is important for the development of collagenase-induced OA pain and disease in mice, with CCL17 thus being a potential therapeutic target for the treatment of the human disease.
Professor John Hamilton is currently Deputy Head, Department of Medicine (RMH), The University of Melbourne and Program Director, Joint Diseases-Basic Sciences, AIMSS. He was Founding Chief Executive Officer, Cooperative Research Centre for Chronic Inflammatory Diseases and Founding Director, Arthritis and Inflammation Research Centre, University of Melbourne.
He was the first non-clinician to be awarded the Parr Rheumatic Prize by the Australian Rheumatology Association for excellence in rheumatology research and the first non-clinician to be awarded their Distinguished Service Medal. He was also the 2nd non-US researcher and 2nd non-clinician to be awarded the American College of Rheumatology Distinguished Basic Investigator Award. He was recently President of the International Association of Inflammation Societies.
He is author of 345 refereed journal publications. His major contributions have been towards the understanding of cytokine-mediated functions of macrophage lineage cells in inflammation/autoimmunity. His research has specific relevance to arthritic disease and pain, in particular, but also has wide implication for many aspects of inflammation and pathology, and therefore for many diseases. Several potential targets for drug intervention and four recent successful Phase II trials in rheumatoid arthritis have arisen from his work.