Abstract
Inflammation and coagulation constitute two host defence systems with complementary physiological roles in limiting tissue damage, restoring homeostasis and eliminating invading pathogens, functions reliant on effective regulation of both processes at a variety of levels. Dysfunctional activation or regulation of either pathway may lead to pathology and contribute to human diseases as diverse as myocardial infarction and septic shock. The serine protease thrombin, a key protein in the coagulation pathway, can activate cellular signalling directly via proteolytic cleavage of the N-terminal domain of a family of G protein-coupled receptors or indirectly through the generation of molecules such as activated protein C. These events transmit signals to many cell types and can elicit the production of various pro-inflammatory mediators such as cytokines, chemokines and growth factors, thereby influencing cell activation, differentiation, survival and migration. This review discusses recent progress in understanding how thrombin and protease-activated receptors influence biological processes, highlighting the detrimental and protective cellular effects of thrombin and its signalling pathways.
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Acknowledgements
Research in A. Dorling's laboratory is funded by the Medical Research Council (award G0801965), Guy's and St Thomas' Charity (R090741) and Novartis, via an unrestricted educational grant. The authors acknowledge the support of the MRC Centre for Transplantation and the additional financial support from the Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust in partnership with the King's College London and King's College Hospital NHS Foundation Trust.
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This article is published as part of the Special Issue on Coagulation & Inflammation [34:1].
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Ma, L., Dorling, A. The roles of thrombin and protease-activated receptors in inflammation. Semin Immunopathol 34, 63–72 (2012). https://doi.org/10.1007/s00281-011-0281-9
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DOI: https://doi.org/10.1007/s00281-011-0281-9