title: Cyclical mechanical stretch enhances degranulation and IL-4 secretion in RBL-2H3 mast cells.
abstract: Mast cells are widely distributed in the body and affect their surrounding environment through degranulation and secretion of cytokines. Conversely, mast cells are influenced by environmental stimuli such as cyclical mechanical stretch (CMS), such as that induced by heartbeat and respiration. Peripherally distributed mast cells are surrounded by extracellular matrix, where they bind IgE on their surface by expressing the high-affinity Fc receptor for IgE (FcεRI), and they release mediators after cross-linking of surface-bound IgE by allergen. To analyse how CMS affects mast cell responses, we examined the effect of applying CMS on the behaviour of IgE-bound mast cells (RBL-2H3 cell line) adhering to fibronectin as a substitute for extracellular matrix. We found that CMS enhanced FcεRI-mediated secretion in the presence of antigen (2,4-dinitrophenol-bovine serum albumin). CMS increased expression of IL-4 mRNA and secretion of IL-4 protein. Western blot analysis showed that CMS changes the signal transduction in mitogen-activated protein kinases and AKT, which in turn alters the regulation of IL-4 and increases the secretion of IL-4. These results suggest that CMS modulates the effect of mast cells on inflammation and resultant tissue remodelling. Understanding how CMS affects mast cell responses is crucial for developing therapies to treat mast cell-related diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan; First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Komiyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyake
authors.forename: Kuniya
authors.initials: K
authors.lastname: Asai
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Mizuno
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015550:Cell Degranulation; D002460:Cell Line; D005353:Fibronectins / Q000502:physiology; D007073:Immunoglobulin E / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology / Q000502:physiology*; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D005353:Fibronectins; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E; D001619:beta-N-Acetylhexosaminidases
keywords: cyclical mechanical stretch; cytokines; degranulation; fibronectin; mast cells; signal transduction