Anti-microbial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of Syk kinase
Cetylpyridinium chloride (CPC) is a quaternary ammonium antimicrobial used in numerous personal care products, human food, cosmetic products, and cleaning solutions. Yet, there is minimal published data on CPC effects on eukaryotes, immune signaling, and human health. Previously, it was shown that l...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Journal of Immunotoxicology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/1547691X.2024.2443397 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832584740057645056 |
|---|---|
| author | Bright Obeng Lucas J. Bennett Bailey E. West Dylan J. Wagner Patrick J. Fleming Morgan N. Tasker Madeleine K. Lorenger Dorothy R. Smith Tetiana Systuk Sydni M. Plummer Jeongwon Eom Marissa D. Paine Collin T. Frangos Michael P. Wilczek Juyoung K. Shim Melissa S. Maginnis Julie A. Gosse |
| author_facet | Bright Obeng Lucas J. Bennett Bailey E. West Dylan J. Wagner Patrick J. Fleming Morgan N. Tasker Madeleine K. Lorenger Dorothy R. Smith Tetiana Systuk Sydni M. Plummer Jeongwon Eom Marissa D. Paine Collin T. Frangos Michael P. Wilczek Juyoung K. Shim Melissa S. Maginnis Julie A. Gosse |
| author_sort | Bright Obeng |
| collection | DOAJ |
| description | Cetylpyridinium chloride (CPC) is a quaternary ammonium antimicrobial used in numerous personal care products, human food, cosmetic products, and cleaning solutions. Yet, there is minimal published data on CPC effects on eukaryotes, immune signaling, and human health. Previously, it was shown that low-micromolar CPC inhibits rat mast cell function by inhibiting antigen (Ag)-stimulated Ca2+ mobilization, microtubule polymerization, and degranulation. In the current study, these findings are extended to human mast cells (LAD2); this paper presents data indicating that a mechanism of action for CPC might center on its positively-charged quaternary nitrogen in its pyridinium headgroup. The inhibitory effect of CPC was independent of signaling platform receptor architecture. Tyrosine phosphorylation events are a trigger of Ca2+ mobilization necessary for degranulation. CPC inhibits global tyrosine phosphorylation in Ag-stimulated mast cells. Specifically, CPC inhibits tyrosine phosphorylation of specific key players Syk kinase and LAT, a substrate of Syk. In contrast, CPC did not affect Lyn kinase phosphorylation. Thus, a root mechanism for CPC effect might be electrostatic disruption of particular tyrosine phosphorylation events essential for signaling. This work presented here outlines biochemical mechanisms underlying the effects of CPC on immune signaling. |
| format | Article |
| id | doaj-art-96c66dff755640d992fb72be01980500 |
| institution | Kabale University |
| issn | 1547-691X 1547-6901 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Immunotoxicology |
| spelling | doaj-art-96c66dff755640d992fb72be019805002025-01-27T11:31:01ZengTaylor & Francis GroupJournal of Immunotoxicology1547-691X1547-69012024-12-0121110.1080/1547691X.2024.2443397Anti-microbial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of Syk kinaseBright Obeng0Lucas J. Bennett1Bailey E. West2Dylan J. Wagner3Patrick J. Fleming4Morgan N. Tasker5Madeleine K. Lorenger6Dorothy R. Smith7Tetiana Systuk8Sydni M. Plummer9Jeongwon Eom10Marissa D. Paine11Collin T. Frangos12Michael P. Wilczek13Juyoung K. Shim14Melissa S. Maginnis15Julie A. Gosse16Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Biology, University of Maine Augusta, Augusta, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Biology, University of Maine Augusta, Augusta, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USADepartment of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USACetylpyridinium chloride (CPC) is a quaternary ammonium antimicrobial used in numerous personal care products, human food, cosmetic products, and cleaning solutions. Yet, there is minimal published data on CPC effects on eukaryotes, immune signaling, and human health. Previously, it was shown that low-micromolar CPC inhibits rat mast cell function by inhibiting antigen (Ag)-stimulated Ca2+ mobilization, microtubule polymerization, and degranulation. In the current study, these findings are extended to human mast cells (LAD2); this paper presents data indicating that a mechanism of action for CPC might center on its positively-charged quaternary nitrogen in its pyridinium headgroup. The inhibitory effect of CPC was independent of signaling platform receptor architecture. Tyrosine phosphorylation events are a trigger of Ca2+ mobilization necessary for degranulation. CPC inhibits global tyrosine phosphorylation in Ag-stimulated mast cells. Specifically, CPC inhibits tyrosine phosphorylation of specific key players Syk kinase and LAT, a substrate of Syk. In contrast, CPC did not affect Lyn kinase phosphorylation. Thus, a root mechanism for CPC effect might be electrostatic disruption of particular tyrosine phosphorylation events essential for signaling. This work presented here outlines biochemical mechanisms underlying the effects of CPC on immune signaling.https://www.tandfonline.com/doi/10.1080/1547691X.2024.2443397Mast celltyrosine phosphorylationcetylpyridinium chlorideSyk kinaseLATLyn |
| spellingShingle | Bright Obeng Lucas J. Bennett Bailey E. West Dylan J. Wagner Patrick J. Fleming Morgan N. Tasker Madeleine K. Lorenger Dorothy R. Smith Tetiana Systuk Sydni M. Plummer Jeongwon Eom Marissa D. Paine Collin T. Frangos Michael P. Wilczek Juyoung K. Shim Melissa S. Maginnis Julie A. Gosse Anti-microbial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of Syk kinase Journal of Immunotoxicology Mast cell tyrosine phosphorylation cetylpyridinium chloride Syk kinase LAT Lyn |
| title | Anti-microbial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of Syk kinase |
| title_full | Anti-microbial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of Syk kinase |
| title_fullStr | Anti-microbial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of Syk kinase |
| title_full_unstemmed | Anti-microbial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of Syk kinase |
| title_short | Anti-microbial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of Syk kinase |
| title_sort | anti microbial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of syk kinase |
| topic | Mast cell tyrosine phosphorylation cetylpyridinium chloride Syk kinase LAT Lyn |
| url | https://www.tandfonline.com/doi/10.1080/1547691X.2024.2443397 |
| work_keys_str_mv | AT brightobeng antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT lucasjbennett antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT baileyewest antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT dylanjwagner antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT patrickjfleming antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT morganntasker antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT madeleineklorenger antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT dorothyrsmith antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT tetianasystuk antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT sydnimplummer antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT jeongwoneom antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT marissadpaine antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT collintfrangos antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT michaelpwilczek antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT juyoungkshim antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT melissasmaginnis antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase AT julieagosse antimicrobialcetylpyridiniumchloridesuppressesmastcellfunctionbytargetingtyrosinephosphorylationofsykkinase |