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Title: G-CSF Receptor Blockade Ameliorates Arthritic Pain and Disease.
Austin Authors: Lee, Ming-Chin;McCubbin, James A;Christensen, Anne D;Poole, Daniel P;Rajasekhar, Pradeep;Lieu, TinaMarie;Bunnett, Nigel W;Garcia-Caraballo, Sonia;Erickson, Andelain;Brierley, Stuart M;Saleh, Reem;Achuthan, Adrian;Fleetwood, Andrew J;Anderson, Robin L ;Hamilton, John A;Cook, Andrew D
Affiliation: Department of Surgery, Columbia University, New York, NY 10032.and
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria 3050, Australia
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria 3010, Australia
Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia
Visceral Pain Group, Department of Human Physiology, Flinders University, Bedford Park, South Australia 5042, Australia
School of Cancer Medicine, La Trobe University, Heidelberg, Victoria 3084, Australia
South Australian Health and Medical Research Institute, Adelaide, South Australia 5000, Australia
Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, Adelaide, South Australia 5000, Australia
Issue Date: 1-May-2017 2017-05-01
Publication information: Journal of immunology (Baltimore, Md. : 1950) 2017; 198(9): 3565-3575
Abstract: G-CSF or CSF-3, originally defined as a regulator of granulocyte lineage development via its cell surface receptor (G-CSFR), can play a role in inflammation, and hence in many pathologies, due to its effects on mature lineage populations. Given this, and because pain is an extremely important arthritis symptom, the efficacy of an anti-G-CSFR mAb for arthritic pain and disease was compared with that of a neutrophil-depleting mAb, anti-Ly6G, in both adaptive and innate immune-mediated murine models. Pain and disease were ameliorated in Ag-induced arthritis, zymosan-induced arthritis, and methylated BSA/IL-1 arthritis by both prophylactic and therapeutic anti-G-CSFR mAb treatment, whereas only prophylactic anti-Ly6G mAb treatment was effective. Efficacy for pain and disease correlated with reduced joint neutrophil numbers and, importantly, benefits were noted without necessarily the concomitant reduction in circulating neutrophils. Anti-G-CSFR mAb also suppressed zymosan-induced inflammatory pain. A new G-CSF-driven (methylated BSA/G-CSF) arthritis model was established enabling us to demonstrate that pain was blocked by a cyclooxygenase-2 inhibitor, suggesting an indirect effect on neurons. Correspondingly, dorsal root ganglion neurons cultured in G-CSF failed to respond to G-CSF in vitro, and Csf3r gene expression could not be detected in dorsal root ganglion neurons by single-cell RT-PCR. These data suggest that G-CSFR/G-CSF targeting may be a safe therapeutic strategy for arthritis and other inflammatory conditions, particularly those in which pain is important, as well as for inflammatory pain per se.
DOI: 10.4049/jimmunol.1602127
ORCID: 0000-0002-6609-3524
PubMed URL: 28320832
Type: Journal Article
Appears in Collections:Journal articles

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