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Mediators of Inflammation
Volume 2013, Article ID 165453, 10 pages
Research Article

Induction of Tumor Necrosis Factor (TNF) Release from Subtypes of T Cells by Agonists of Proteinase Activated Receptors

1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 300 Guangzhou Road, Jiangsu 210029, China
2Department of Infectious Diseases, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
3Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, China

Received 2 July 2013; Revised 22 November 2013; Accepted 22 November 2013

Academic Editor: Mohammad Athar

Copyright © 2013 Haiwei Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Serine proteinases have been recognized as playing an important role in inflammation via proteinase activated receptors (PARs). However, little is known about the influence of serine proteinases and PARs on TNF secretion from highly purified T cells. We challenged T cells from human peripheral blood with serine proteinases and agonist peptides of PARs and measured the levels of TNF in culture supernatants by ELISA. The results showed that thrombin and trypsin, but not tryptase, stimulated approximately up to 2.5-fold increase in TNF release from T cells following 16 h incubation. Proteinase inhibitors and PAR-1 antagonist SCH 79797 almost completely abolished thrombin- and trypsin-induced TNF release from T cells. Agonist peptides of PAR-1, but not PAR-2 induced TNF release from T cells. Moreover, trypsin- and thrombin-induced upregulated expression of TNF was observed in CD4+, IL-4+, or CD25+ T cells, but not in IFN+ or IL-17+ T cells. The signaling pathways MAPK/ERK and PI3K/Akt are involved in the thrombin- and trypsin-induced TNF release from T cells. In conclusion, thrombin and trypsin can induce TNF release from IL-4+ and CD25+ T cells through activation of PAR-1 and therefore contribute to regulation of immune response and inflammation of the body.