Constitutive activation of mitogen activated protein kinase (MAPK) leads to IL-6 and Rantes over-production in thymic epithelial cells (TEC) of patients with myasthenia gravis (MG)

Cytokines have been implicated in MG-associated thymic pathology (thymic hyperplasia and thymoma). Thymic epithelium is a major producer of cytokines or chemochines. By comparing IL-6 and Rantes production of TEC cultures of normal and hyperplastic MG-thymus we found that: 1) MG-TEC over-produced IL-6 basally, and both IL-6 and Rantes upon M integrin-cross-linking or thymocyte adhesion; 2) transcription and phosphorylation of MAPKs and binding activity of NF-kappaB, all known regulator of IL-6 and Rantes gene expression, were basally increased in MG-TEC; 3) Rantes and IL-6 increased respectively migration and survival of peripheral B and T cells of MG patients. We propose that the abnormal secretion of Rantes and IL-6 by MG TEC may be of patho genetic relevance in MG-associated thymic disorders.