S100A8 & S100A9: alarmin mediated inflammation in tendinopathy

Crowe, L. A.N. et al. (2019) S100A8 & S100A9: alarmin mediated inflammation in tendinopathy. Scientific Reports, 9(1), 1463. (doi: 10.1038/s41598-018-37684-3) (PMID:30728384) (PMCID:PMC6365574)

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Alarmins S100A8 and S100A9 are endogenous molecules released in response to environmental triggers and cellular damage. They are constitutively expressed in immune cells such as monocytes and neutrophils and their expression is upregulated under inflammatory conditions. The molecular mechanisms that regulate inflammatory pathways in tendinopathy are largely unknown therefore identifying early immune effectors is essential to understanding the pathology. Based on our previous investigations highlighting tendinopathy as an alarmin mediated pathology we sought evidence of S100A8 & A9 expression in a human model of tendinopathy and thereafter, to explore mechanisms whereby S100 proteins may regulate release of inflammatory mediators and matrix synthesis in human tenocytes. Immunohistochemistry and quantitative RT-PCR showed S100A8 & A9 expression was significantly upregulated in tendinopathic tissue compared with control. Furthermore, treating primary human tenocytes with exogenous S100A8 & A9 significantly increased protein release of IL-6, IL-8, CCL2, CCL20 and CXCL10; however, no alterations in genes associated with matrix remodelling were observed at a transcript level. We propose S100A8 & A9 participate in early pathology by modulating the stromal microenvironment and influencing the inflammatory profile observed in tendinopathy. S100A8 and S100A9 may participate in a positive feedback mechanism involving enhanced leukocyte recruitment and release of pro-inflammatory cytokines from tenocytes that perpetuates the inflammatory response within the tendon in the early stages of disease.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Reilly, Mr James and Millar, Professor Neal and Kitson, Miss Susan and Akbar, Mr Moeed and McLean, Michael and Crowe, Ms Lindsay and Garcia Melchor, Dr Emma
Authors: Crowe, L. A.N., McLean, M., Kitson, S. M., Garcia Melchor, E., Patommel, K., Cao, H. M., Reilly, J. H., Leach, W. J., Rooney, B. P., Spencer, S. J., Mullen, M., Chambers, M., Murrell, G. A.C., McInnes, I. B., Akbar, M., and Millar, N. L.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Scientific Reports 9(1):1463
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190660MRC Doctoral Training Grant 2013/14 and 2014/15George BaillieMedical Research Council (MRC)MR/K501335/1MVLS - Graduate School
301515Damage mechanisms in tendon diseaseNeal MillarMedical Research Council (MRC)MR/R020515/1III - Immunology
173463HMGB1: a key damage mediator in tendinopathyNeal MillarVersus Arthritis (ARTRESUK)21346III - Immunology