IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy.
Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in 'early tendinopathy' compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders.
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow, Scotland UK.
Neal L
NL
Millar
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow, Scotland UK.
Moeed
M
Akbar
Department of Orthopaedic Surgery, NYU School of Medicine, New York, USA.
Abigail L
AL
Campbell
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow, Scotland UK.
James H
JH
Reilly
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow, Scotland UK.
Shauna C
SC
Kerr
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow, Scotland UK.
Michael
M
McLean
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow, Scotland UK.
Marina
M
Frleta-Gilchrist
Department of Orthopaedic Surgery, Queen Elizabeth University Hospital, Glasgow, Scotland, UK.
Umberto G
UG
Fazzi
Department of Orthopaedic Surgery, Queen Elizabeth University Hospital, Glasgow, Scotland, UK.
William J
WJ
Leach
Department of Orthopaedic Surgery, Queen Elizabeth University Hospital, Glasgow, Scotland, UK.
Brian P
BP
Rooney
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow, Scotland UK.
Lindsay A N
LA
Crowe
Orthopaedic Research Institute, Department of Orthopaedic Surgery, St George Hospital Campus, University of New South Wales, Australia.
George A C
GA
Murrell
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow, Scotland UK.
Iain B
IB
McInnes
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D000070636:Rotator Cuff Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D052256:Tendinopathy / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000070916:Tenocytes / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
D016207:Cytokines; C508717:IL17A protein, human; D020381:Interleukin-17