Dataset Information

Involvement of class II phosphoinositide 3-kinase ?-isoform in antigen-induced degranulation in RBL-2H3 cells.

ABSTRACT: In this study, we present findings that suggest that PI3K-C2?, a member of the class II phosphoinositide 3-kinase (PI3K) subfamily, regulates the process of Fc?RI-triggered degranulation. RBL-2H3 cells were transfected with shRNA targeting PI3K-C2?. The knockdown impaired the Fc?RI-induced release of a lysosome enzyme, ?-hexosaminidase, without affecting the intracellular Ca2+ mobilization. The release of mRFP-tagged neuropeptide-Y, a reporter for the regulated exocytosis, was also decreased in the PI3K-C2?-deficient cells. The release was increased significantly by the expression of the siRNA-resistant version of PI3K-C2?. In wild-type cells, Fc?RI stimulation induced the formation of large vesicles, which were associated with CD63, a marker protein of secretory granules. On the vesicles, the existence of PI3K-C2? and PtdIns(3,4)P2 was observed. These results indicated that PI3K-C2? and its product PtdIns(3,4)P2 may play roles in the secretory process.

SUBMITTER: Nigorikawa K

PROVIDER: S-EPMC4214793 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Involvement of class II phosphoinositide 3-kinase α-isoform in antigen-induced degranulation in RBL-2H3 cells.

Nigorikawa Kiyomi K Hazeki Kaoru K Guo Ying Y Hazeki Osamu O

PloS one 20141030 10

In this study, we present findings that suggest that PI3K-C2α, a member of the class II phosphoinositide 3-kinase (PI3K) subfamily, regulates the process of FcεRI-triggered degranulation. RBL-2H3 cells were transfected with shRNA targeting PI3K-C2α. The knockdown impaired the FcεRI-induced release of a lysosome enzyme, β-hexosaminidase, without affecting the intracellular Ca2+ mobilization. The release of mRFP-tagged neuropeptide-Y, a reporter for the regulated exocytosis, was also decreased in ...[more]

PMID: 25357130

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Project description:Mast cells and basophils are central players in allergic reactions triggered by immunoglobulin E (IgE). They have intracellular granules containing allergic mediators (e.g., histamine, serotonin, inflammatory cytokines, proteases and ?-hexosaminidase), and stimulation by IgE-allergen complex leads to the release of such allergic mediators from the granules, that is, degranulation. Mast cells are residents of mucosal surfaces, including those of nasal and oral cavities, and play an important role in the innate defense system. Members of the mitis group streptococci such as Streptococcus oralis, are primary colonizers of the human oral cavity. They produce hydrogen peroxide (H2O2) as a by-product of sugar metabolism. In this study, we investigated the effects of streptococcal infection on RBL-2H3 mast cell/basophil cell line. Infection by oral streptococci did not induce degranulation of the cells. Stimulation of the RBL-2H3 cells with anti-dinitrophenol (DNP) IgE and DNP-conjugated human serum albumin triggers degranulation with the release of ?-hexosaminidase. We found that S. oralis and other mitis group streptococci inhibited the IgE-triggered degranulation of RBL-2H3 cells. Since mitis group streptococci produce H2O2, we examined the effect of S. oralis mutant strain deficient in producing H2O2, and found that they lost the ability to suppress the degranulation. Moreover, H2O2 alone inhibited the IgE-induced degranulation. Subsequent analysis suggested that the inhibition of degranulation was related to the cytotoxicity of streptococcal H2O2. Activated RBL-2H3 cells produce interleukin-4 (IL-4); however, IL-4 production was not induced by streptococcal H2O2. Furthermore, an in vivo study using the murine pollen-induced allergic rhinitis model suggested that the streptococcal H2O2 reduces nasal allergic reaction. These findings reveal that H2O2 produced by oral mitis group streptococci inhibits IgE-stimulated degranulation by inducing cell death. Consequently, streptococcal H2O2 can be considered to modulate the allergic reaction in mucosal surfaces.

Dataset Information

Involvement of class II phosphoinositide 3-kinase ?-isoform in antigen-induced degranulation in RBL-2H3 cells.

Publications

Involvement of class II phosphoinositide 3-kinase α-isoform in antigen-induced degranulation in RBL-2H3 cells.

Similar Datasets

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