Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome.
Ethanol has multiple effects on biochemical events in a variety of cell types, including the high-affinity immunoglobulin E receptor (FcεRI) signaling in antigen-activated mast cells. However, the underlying molecular mechanism remains unknown. To get better understanding of the effect of ethanol on...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144596&type=printable |
| _version_ | 1826584325343150080 |
|---|---|
| author | Lubica Draberova Tomas Paulenda Ivana Halova Lucie Potuckova Viktor Bugajev Monika Bambouskova Magda Tumova Petr Draber |
| author_facet | Lubica Draberova Tomas Paulenda Ivana Halova Lucie Potuckova Viktor Bugajev Monika Bambouskova Magda Tumova Petr Draber |
| author_sort | Lubica Draberova |
| collection | DOAJ |
| description | Ethanol has multiple effects on biochemical events in a variety of cell types, including the high-affinity immunoglobulin E receptor (FcεRI) signaling in antigen-activated mast cells. However, the underlying molecular mechanism remains unknown. To get better understanding of the effect of ethanol on FcεRI-mediated signaling we examined the effect of short-term treatment with non-toxic concentrations of ethanol on FcεRI signaling events in mouse bone marrow-derived mast cells. We found that 15 min exposure to ethanol inhibited antigen-induced degranulation, calcium mobilization, expression of proinflammatory cytokine genes (tumor necrosis factor-α, interleukin-6, and interleukin-13), and formation of reactive oxygen species in a dose-dependent manner. Removal of cellular cholesterol with methyl-β-cyclodextrin had a similar effect and potentiated some of the inhibitory effects of ethanol. In contrast, exposure of the cells to cholesterol-saturated methyl-β-cyclodextrin abolished in part the inhibitory effect of ethanol on calcium response and production of reactive oxygen species, supporting lipid-centric theories of ethanol action on the earliest stages of mast cell signaling. Further studies showed that exposure to ethanol and/or removal of cholesterol inhibited early FcεRI activation events, including tyrosine phosphorylation of the FcεRI β and γ subunits, SYK kinases, LAT adaptor protein, phospholipase Cγ, STAT5, and AKT and internalization of aggregated FcεRI. Interestingly, ethanol alone, and particularly in combination with methyl-β-cyclodextrin, enhanced phosphorylation of negative regulatory tyrosine 507 of LYN kinase. Finally, we found that ethanol reduced passive cutaneous anaphylactic reaction in mice, suggesting that ethanol also inhibits FcεRI signaling under in vivo conditions. The combined data indicate that ethanol interferes with early antigen-induced signaling events in mast cells by suppressing the function of FcεRI-cholesterol signalosomes at the plasma membrane. |
| first_indexed | 2024-12-10T08:20:30Z |
| format | Article |
| id | doaj.art-b80b828ae57f47ab897b2cee161bd25f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T15:35:57Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b80b828ae57f47ab897b2cee161bd25f2025-02-25T05:33:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014459610.1371/journal.pone.0144596Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome.Lubica DraberovaTomas PaulendaIvana HalovaLucie PotuckovaViktor BugajevMonika BambouskovaMagda TumovaPetr DraberEthanol has multiple effects on biochemical events in a variety of cell types, including the high-affinity immunoglobulin E receptor (FcεRI) signaling in antigen-activated mast cells. However, the underlying molecular mechanism remains unknown. To get better understanding of the effect of ethanol on FcεRI-mediated signaling we examined the effect of short-term treatment with non-toxic concentrations of ethanol on FcεRI signaling events in mouse bone marrow-derived mast cells. We found that 15 min exposure to ethanol inhibited antigen-induced degranulation, calcium mobilization, expression of proinflammatory cytokine genes (tumor necrosis factor-α, interleukin-6, and interleukin-13), and formation of reactive oxygen species in a dose-dependent manner. Removal of cellular cholesterol with methyl-β-cyclodextrin had a similar effect and potentiated some of the inhibitory effects of ethanol. In contrast, exposure of the cells to cholesterol-saturated methyl-β-cyclodextrin abolished in part the inhibitory effect of ethanol on calcium response and production of reactive oxygen species, supporting lipid-centric theories of ethanol action on the earliest stages of mast cell signaling. Further studies showed that exposure to ethanol and/or removal of cholesterol inhibited early FcεRI activation events, including tyrosine phosphorylation of the FcεRI β and γ subunits, SYK kinases, LAT adaptor protein, phospholipase Cγ, STAT5, and AKT and internalization of aggregated FcεRI. Interestingly, ethanol alone, and particularly in combination with methyl-β-cyclodextrin, enhanced phosphorylation of negative regulatory tyrosine 507 of LYN kinase. Finally, we found that ethanol reduced passive cutaneous anaphylactic reaction in mice, suggesting that ethanol also inhibits FcεRI signaling under in vivo conditions. The combined data indicate that ethanol interferes with early antigen-induced signaling events in mast cells by suppressing the function of FcεRI-cholesterol signalosomes at the plasma membrane.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144596&type=printable |
| spellingShingle | Lubica Draberova Tomas Paulenda Ivana Halova Lucie Potuckova Viktor Bugajev Monika Bambouskova Magda Tumova Petr Draber Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome. PLoS ONE |
| title | Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome. |
| title_full | Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome. |
| title_fullStr | Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome. |
| title_full_unstemmed | Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome. |
| title_short | Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome. |
| title_sort | ethanol inhibits high affinity immunoglobulin e receptor fcεri signaling in mast cells by suppressing the function of fcεri cholesterol signalosome |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144596&type=printable |
| work_keys_str_mv | AT lubicadraberova ethanolinhibitshighaffinityimmunoglobulinereceptorfcerisignalinginmastcellsbysuppressingthefunctionoffcericholesterolsignalosome AT tomaspaulenda ethanolinhibitshighaffinityimmunoglobulinereceptorfcerisignalinginmastcellsbysuppressingthefunctionoffcericholesterolsignalosome AT ivanahalova ethanolinhibitshighaffinityimmunoglobulinereceptorfcerisignalinginmastcellsbysuppressingthefunctionoffcericholesterolsignalosome AT luciepotuckova ethanolinhibitshighaffinityimmunoglobulinereceptorfcerisignalinginmastcellsbysuppressingthefunctionoffcericholesterolsignalosome AT viktorbugajev ethanolinhibitshighaffinityimmunoglobulinereceptorfcerisignalinginmastcellsbysuppressingthefunctionoffcericholesterolsignalosome AT monikabambouskova ethanolinhibitshighaffinityimmunoglobulinereceptorfcerisignalinginmastcellsbysuppressingthefunctionoffcericholesterolsignalosome AT magdatumova ethanolinhibitshighaffinityimmunoglobulinereceptorfcerisignalinginmastcellsbysuppressingthefunctionoffcericholesterolsignalosome AT petrdraber ethanolinhibitshighaffinityimmunoglobulinereceptorfcerisignalinginmastcellsbysuppressingthefunctionoffcericholesterolsignalosome |