IL-21 receptor expression in human tendinopathy.
The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward an early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly upregulated by proinflammatory cytokines (TNFα/IL-1β) in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression, these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy.
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, 120 University Avenue, Glasgow G12 8TA, UK ; Columbia University College of Physicians & Surgeons, New York, NY, USA.
Abigail L
AL
Campbell
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, 120 University Avenue, Glasgow G12 8TA, UK.
Nicola C
NC
Smith
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, 120 University Avenue, Glasgow G12 8TA, UK.
James H
JH
Reilly
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, 120 University Avenue, Glasgow G12 8TA, UK.
Shauna C
SC
Kerr
Department of Orthopaedic Surgery, Western Infirmary, Glasgow, UK.
William J
WJ
Leach
Department of Orthopaedic Surgery, Western Infirmary, Glasgow, UK.
Umberto G
UG
Fazzi
Department of Orthopaedic Surgery, Western Infirmary, Glasgow, UK.
Brian P
BP
Rooney
Department of Orthopaedic Surgery, Orthopaedic Research Institute, University of New South Wales, St George Hospital Campus, Sydney, NSW, Australia.
George A C
GA
Murrell
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, 120 University Avenue, Glasgow G12 8TA, UK ; Department of Orthopaedic Surgery, Western Infirmary, Glasgow, UK.
Neal L
NL
Millar
D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000166:cytology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D053655:Receptors, Interleukin-21 / Q000378:metabolism*; D000070636:Rotator Cuff Injuries; D052256:Tendinopathy / Q000378:metabolism*; D013710:Tendons / Q000473:pathology; D055815:Young Adult
D053655:Receptors, Interleukin-21