HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Colombara, M. Articles by Ramarli, D. Search for Related Content PubMed PubMed Citation Articles by Colombara, M. Articles by Ramarli, D.

Constitutive Activation of p38 and ERK1/2 MAPKs in Epithelial Cells of Myasthenic Thymus Leads to IL-6 and RANTES Overexpression: Effects on Survival and Migration of Peripheral T and B Cells¹

Michaela Colombara^*, Valeria Antonini^2,*, Anna Pia Riviera^2,*,, Fabrizio Mainiero, Raffaele Strippoli, Marcello Merola, Giulio Fracasso^*, Ornella Poffe^*,, Nadia Brutti^*,, Giuseppe Tridente^*,, Marco Colombatti^* and Dunia Ramarli^3,*,

^* Section of Immunology, Department of Pathology, and Section of Biochemistry, Department of Neurological and Vision Sciences, University of Verona, Verona, Italy; Clinical Immunology, G. B. Rossi Hospital, Verona, Italy; and Department of Experimental Medicine and Pathology, Institute Pasteur-Fondazione, Cenci Bolognetti, University of Rome, "La Sapienza," Italy

Myasthenia gravis (MG) is an autoimmune disease of neuromuscular junctions where thymus plays a pathogenetic role. Thymectomy benefits patients, and thymic hyperplasia, a lymphoid infiltration of perivascular spaces becoming site of autoantibody production, is recurrently observed. Cytokines and chemokines, produced by thymic epithelium and supporting survival and migration of T and B cells, are likely to be of great relevance in pathogenesis of thymic hyperplasia. In thymic epithelial cell (TEC) cultures derived "in vitro" from normal or hyperplastic age-matched MG thymuses, we demonstrate by gene profiling analysis that MG-TEC basally overexpress genes coding for p38 and ERK1/2 MAPKs and for components of their signaling pathways. Immunoblotting experiments confirmed that p38 and ERK1/2 proteins were overexpressed in MG-TEC and, in addition, constitutively activated. Pharmacological blockage with specific inhibitors confirmed their role in the control of IL-6 and RANTES gene expression. According to our results, IL-6 and RANTES levels were abnormally augmented in MG-TEC, either basally or upon induction by adhesion-related stimuli. The finding that IL-6 and RANTES modulate, respectively, survival and migration of peripheral lymphocytes of myasthenic patients point to MAPK transcriptional and posttranscriptional abnormalities of MG-TEC as a key step in the pathological remodelling of myasthenic thymus.