Impaired mast cell activation in gene-targeted mice lacking the serum- and glucocorticoid-inducible kinase SGK1
| Autor: | Malgorzata Sobiesiak, Tilo Biedermann, Ekaterina Shumilina, Susanne Kaesler, Adrian Lupescu, Florian Lang, Dietmar Kuhl, Martin Schaller, Florian Wölbing, Irina M. Zemtsova, Rebecca S. Lam, Nicole Matzner, Naima Zahir |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Immunology Stimulation Bone Marrow Cells Biology Protein Serine-Threonine Kinases Immediate-Early Proteins chemistry.chemical_compound Mice Phosphatidylinositol 3-Kinases Potassium Channels Calcium-Activated Internal medicine medicine Immunology and Allergy Animals Mast Cells Receptor Anaphylaxis Cells Cultured Mice Knockout urogenital system Degranulation Mast cell Mice Inbred C57BL medicine.anatomical_structure Endocrinology chemistry Ionomycin Gene Targeting SGK1 Female Intracellular Histamine |
| Zdroj: | ResearcherID |
| ISSN: | 1550-6606 |
| Popis: | The PI3K pathway plays a pivotal role in the stimulation of mast cells. PI3K-dependent kinases include the serum- and glucocorticoid-inducible kinase 1 (SGK1). The present study explored the role of SGK1 in mast cell function. Mast cells were isolated from bone marrow (BMMC) of SGK1 knockout mice ( sgk1 −/− ) and their wild-type littermates ( sgk1 +/+ ). The BMMC number as well as CD117, CD34, and FceRI expression in BMCCs were similar in both genotypes. Upon Ag stimulation of the FceRI receptor, Ca 2+ entry but not Ca 2+ release from intracellular stores was markedly impaired in sgk1 −/− BMMCs. The currents through Ca 2+ -activated K + channels induced by Ag were significantly higher in sgk1 +/+ BMMCs than in sgk1 −/− BMMCs. Treatment with the Ca 2+ ionophore ionomycin (1 μM) led to activation of the K + channels in both genotypes, indicating that the Ca 2+ -activated K + channels are similarly expressed and sensitive to activation by Ca 2+ in sgk1 +/+ and sgk1 −/− BMMCs, and that blunted stimulation of Ca 2+ -activated K + channels was secondary to decreased Ca 2+ entry. Ag-IgE-induced degranulation and early IL-6 secretion were also significantly blunted in sgk1 −/− BMMCs. The decrease in body temperature following Ag treatment, which reflects an anaphylactic reaction, was substantially reduced in sgk1 −/− mice, pointing to impaired mast cell function in vivo. Serum histamine levels measured 30 min after induction of an anaphylactic reaction were significantly lower in sgk1 −/− than in sgk1 +/+ mice. The observations reveal a critical role for SGK1 in ion channel regulation and the function of mast cells, and thus disclose a completely novel player in the regulation of allergic reaction. |
| Databáze: | OpenAIRE |
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