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

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...

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Main Authors: Haiwei Yang, Tao Li, Jifu Wei, Huiyun Zhang, Shaoheng He
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/165453
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author Haiwei Yang
Tao Li
Jifu Wei
Huiyun Zhang
Shaoheng He
author_facet Haiwei Yang
Tao Li
Jifu Wei
Huiyun Zhang
Shaoheng He
author_sort Haiwei Yang
collection DOAJ
description 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.
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series Mediators of Inflammation
spelling doaj-art-844678ea2de246ccb40d3e326270ebd72025-08-20T03:37:11ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/165453165453Induction of Tumor Necrosis Factor (TNF) Release from Subtypes of T Cells by Agonists of Proteinase Activated ReceptorsHaiwei Yang0Tao Li1Jifu Wei2Huiyun Zhang3Shaoheng He4Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 300 Guangzhou Road, Jiangsu 210029, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, ChinaDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 300 Guangzhou Road, Jiangsu 210029, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, ChinaDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 300 Guangzhou Road, Jiangsu 210029, ChinaSerine 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.http://dx.doi.org/10.1155/2013/165453
spellingShingle Haiwei Yang
Tao Li
Jifu Wei
Huiyun Zhang
Shaoheng He
Induction of Tumor Necrosis Factor (TNF) Release from Subtypes of T Cells by Agonists of Proteinase Activated Receptors
Mediators of Inflammation
title Induction of Tumor Necrosis Factor (TNF) Release from Subtypes of T Cells by Agonists of Proteinase Activated Receptors
title_full Induction of Tumor Necrosis Factor (TNF) Release from Subtypes of T Cells by Agonists of Proteinase Activated Receptors
title_fullStr Induction of Tumor Necrosis Factor (TNF) Release from Subtypes of T Cells by Agonists of Proteinase Activated Receptors
title_full_unstemmed Induction of Tumor Necrosis Factor (TNF) Release from Subtypes of T Cells by Agonists of Proteinase Activated Receptors
title_short Induction of Tumor Necrosis Factor (TNF) Release from Subtypes of T Cells by Agonists of Proteinase Activated Receptors
title_sort induction of tumor necrosis factor tnf release from subtypes of t cells by agonists of proteinase activated receptors
url http://dx.doi.org/10.1155/2013/165453
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