Increased Expression of Genes Linked to FcεRI Signaling and to Cytokine and Chemokine Production in Lyn-Deficient Mast Cells
| Autor: | Julie A. Wilder, Valerie Hernandez-Hansen, Janet M. Oliver, Christy A. Tarleton, Julie D. J. Bard, Bridget S. Wilson, Clifford A. Lowell |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Chemokine
medicine.medical_treatment Immunology CCL1 Proinflammatory cytokine Mice FYN LYN medicine Animals Immunology and Allergy Mast Cells RNA Messenger Antigens Inflammation Mice Knockout biology Receptors IgE Gene Expression Profiling hemic and immune systems Cell biology src-Family Kinases CCL9 Cytokine Gene Expression Regulation biology.protein Cytokines Chemokines biological phenomena cell phenomena and immunity Signal transduction Signal Transduction |
| Zdroj: | The Journal of Immunology. 175:7880-7888 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.175.12.7880 |
| Popis: | Cross-linking the high-affinity IgE receptor, FcεRI, on mast cells activates signaling pathways leading to the release of preformed inflammatory mediators and the production of cytokines and chemokines associated with allergic disorders. Bone marrow-derived mast cells (BMMCs) from Lyn-deficient (Lyn−/−) mice are hyperresponsive to FcεRI cross-linking with multivalent Ag. Previous studies linked the hyperresponsive phenotype in part to increased Fyn kinase activity and reduced SHIP phosphatase activity in the Lyn−/− BMMCs in comparison with wild-type (WT) cells. In this study, we compared gene expression profiles between resting and Ag-activated WT and Lyn−/− BMMCs to identify other factors that may contribute to the hyperresponsiveness of the Lyn−/− cells. Among genes implicated in the positive regulation of FcεRI signaling, mRNA for the tyrosine kinase, Fyn, and for several proteins contributing to calcium regulation are more up-regulated following Ag stimulation in Lyn−/− BMMCs than in WT BMMCs. Conversely, mRNA for the low-affinity IgG receptor (FcγRIIB), implicated in negative regulation of FcεRI-mediated signaling, is more down-regulated in Ag-stimulated Lyn−/− BMMCs than in WT BMMCs. Genes coding for proinflammatory cytokines and chemokines (IL-4, IL-6, IL-13, CSF, CCL1, CCL3, CCL5, CCL7, CCL9, and MIP1β)are all more highly expressed in Ag-stimulated Lyn−/− mast cells than in WT cells. These microarray data identify Lyn as a negative regulator in Ag-stimulated BMMCs of the expression of genes linked to FcεRI signaling and also to the response pathways that lead to allergy and asthma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|