BACKGROUND: T-cell infiltration of submucosa, release of proinflammatory cytokines leading to epithelial activation, and contributions to inflammation are observed in chronic rhinosinusitis (CRS). OBJECTIVES: Molecular mechanisms and kinetics of T-cell interaction with sinus epithelium leading to activation followed by subsequent apoptosis of epithelial cells were the focus of the current study. METHODS: Primary human sinus epithelial cells and T cells generated from sinus tissues of healthy individuals and patients with CRS with or without allergy and sinus tissue biopsies were characterized in terms of activation (surface marker expression, cytokine production via real-time PCR, confocal microscopy, ELISA) and apoptosis (annexin V/7-amino-actinomycin D staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, receptor expression by flow cytometry, confocal microscopy) of epithelial cells. RESULTS: Primary human sinus epithelial cells isolated from patients with CRS were at an activated state with upregulated expression of HLA-DR, IFN-gamma-inducible protein 10, monokine induced by IFN-gamma, and TNF-related apoptosis-inducing ligand (TRAIL) compared with healthy individuals. The expressions of these chemokines, HLA-DR, TRAIL, and TNF receptor 2 were significantly induced by IFN-gamma, whereas TRAIL receptor 4 was downregulated. Epithelial cells started to undergo apoptosis 48 hours after IFN-gamma stimulation when the transcription of proinflammatory cytokines and chemokines decreased to initial levels. The essential factors for sinus epithelial apoptosis were T(H)1 cells and IFN-gamma. Epithelial apoptosis was enhanced by Fas-Fas-ligand and TRAIL-TRAIL receptor 2 interactions. Remarkable apoptosis of epithelial cells and shedding was observed in CRS in situ. CONCLUSION: Epithelial cell interaction with activated T cells is a biphasic phenomenon in CRS. Initially activated T cells lead to activation and induction of proinflammatory functions of epithelial cells, and thereafter their apoptotic death, resulting in no more contribution to inflammation, takes place.
BACKGROUND: T-cell infiltration of submucosa, release of proinflammatory cytokines leading to epithelial activation, and contributions to inflammation are observed in chronic rhinosinusitis (CRS). OBJECTIVES: Molecular mechanisms and kinetics of T-cell interaction with sinus epithelium leading to activation followed by subsequent apoptosis of epithelial cells were the focus of the current study. METHODS: Primary human sinus epithelial cells and T cells generated from sinus tissues of healthy individuals and patients with CRS with or without allergy and sinus tissue biopsies were characterized in terms of activation (surface marker expression, cytokine production via real-time PCR, confocal microscopy, ELISA) and apoptosis (annexin V/7-amino-actinomycin D staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, receptor expression by flow cytometry, confocal microscopy) of epithelial cells. RESULTS: Primary human sinus epithelial cells isolated from patients with CRS were at an activated state with upregulated expression of HLA-DR, IFN-gamma-inducible protein 10, monokine induced by IFN-gamma, and TNF-related apoptosis-inducing ligand (TRAIL) compared with healthy individuals. The expressions of these chemokines, HLA-DR, TRAIL, and TNF receptor 2 were significantly induced by IFN-gamma, whereas TRAIL receptor 4 was downregulated. Epithelial cells started to undergo apoptosis 48 hours after IFN-gamma stimulation when the transcription of proinflammatory cytokines and chemokines decreased to initial levels. The essential factors for sinus epithelial apoptosis were T(H)1 cells and IFN-gamma. Epithelial apoptosis was enhanced by Fas-Fas-ligand and TRAIL-TRAIL receptor 2 interactions. Remarkable apoptosis of epithelial cells and shedding was observed in CRS in situ. CONCLUSION: Epithelial cell interaction with activated T cells is a biphasic phenomenon in CRS. Initially activated T cells lead to activation and induction of proinflammatory functions of epithelial cells, and thereafter their apoptotic death, resulting in no more contribution to inflammation, takes place.
Authors: Cezmi A Akdis; Claus Bachert; Cemal Cingi; Mark S Dykewicz; Peter W Hellings; Robert M Naclerio; Robert P Schleimer; Dennis Ledford Journal: J Allergy Clin Immunol Date: 2013-04-12 Impact factor: 10.793
Authors: Michael B Soyka; David Holzmann; Tomasz M Basinski; Marcin Wawrzyniak; Christina Bannert; Simone Bürgler; Tunc Akkoc; Angela Treis; Beate Rückert; Mübeccel Akdis; Cezmi A Akdis; Thomas Eiwegger Journal: PLoS One Date: 2015-05-01 Impact factor: 3.240
Authors: Nikolaos G Papadopoulos; Ioana Agache; Sevim Bavbek; Beatrice M Bilo; Fulvio Braido; Victoria Cardona; Adnan Custovic; Jan Demonchy; Pascal Demoly; Philippe Eigenmann; Jacques Gayraud; Clive Grattan; Enrico Heffler; Peter W Hellings; Marek Jutel; Edward Knol; Jan Lötvall; Antonella Muraro; Lars K Poulsen; Graham Roberts; Peter Schmid-Grendelmeier; Chrysanthi Skevaki; Massimo Triggiani; Ronald Vanree; Thomas Werfel; Breda Flood; Susanna Palkonen; Roberta Savli; Pia Allegri; Isabella Annesi-Maesano; Francesco Annunziato; Dario Antolin-Amerigo; Christian Apfelbacher; Miguel Blanca; Ewa Bogacka; Patrizia Bonadonna; Matteo Bonini; Onur Boyman; Knut Brockow; Peter Burney; Jeroen Buters; Indre Butiene; Moises Calderon; Lars Olaf Cardell; Jean-Christoph Caubet; Sevcan Celenk; Ewa Cichocka-Jarosz; Cemal Cingi; Mariana Couto; Nicolette Dejong; Stefano Del Giacco; Nikolaos Douladiris; Filippo Fassio; Jean-Luc Fauquert; Javier Fernandez; Montserrat Fernandez Rivas; Marta Ferrer; Carsten Flohr; James Gardner; Jon Genuneit; Philippe Gevaert; Anna Groblewska; Eckard Hamelmann; Hans Jürgen Hoffmann; Karin Hoffmann-Sommergruber; Lilit Hovhannisyan; Valérie Hox; Frode L Jahnsen; Omer Kalayci; Ayse Füsun Kalpaklioglu; Jörg Kleine-Tebbe; George Konstantinou; Marcin Kurowski; Susanne Lau; Roger Lauener; Antti Lauerma; Kirsty Logan; Antoine Magnan; Joanna Makowska; Heidi Makrinioti; Paraskevi Mangina; Felicia Manole; Adriano Mari; Angel Mazon; Clare Mills; Ervinç Mingomataj; Bodo Niggemann; Gunnar Nilsson; Markus Ollert; Liam O'Mahony; Serena O'Neil; Gianni Pala; Alberto Papi; Gianni Passalacqua; Michael Perkin; Oliver Pfaar; Constantinos Pitsios; Santiago Quirce; Ulrike Raap; Monika Raulf-Heimsoth; Claudio Rhyner; Paula Robson-Ansley; Rodrigo Rodrigues Alves; Zeljka Roje; Carmen Rondon; Odilija Rudzeviciene; Franziska Ruëff; Maia Rukhadze; Gabriele Rumi; Cansin Sackesen; Alexandra F Santos; Annalisa Santucci; Christian Scharf; Carsten Schmidt-Weber; Benno Schnyder; Jürgen Schwarze; Gianenrico Senna; Svetlana Sergejeva; Sven Seys; Andrea Siracusa; Isabel Skypala; Milena Sokolowska; Francois Spertini; Radoslaw Spiewak; Aline Sprikkelman; Gunter Sturm; Ines Swoboda; Ingrid Terreehorst; Elina Toskala; Claudia Traidl-Hoffmann; Carina Venter; Berber Vlieg-Boerstra; Paul Whitacker; Margitta Worm; Paraskevi Xepapadaki; Cezmi A Akdis Journal: Clin Transl Allergy Date: 2012-11-02 Impact factor: 5.871