Resolvin D2 and Resolvin D1 Differentially Activate Protein Kinases to Counter-Regulate Histamine-Induced [Ca<sup>2+</sup>]<sub>i</sub> Increase and Mucin Secretion in Conjunctival Goblet Cells
Resolvin (Rv) D2 and RvD1 are biosynthesized from docosahexaenoic acid (DHA) and promote resolution of inflammation in multiple organs and tissues, including the conjunctiva. Histamine is a mediator produced by mast cells in the conjunctiva during the allergic response. We determined the interaction...
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/1/141 |
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| author | Menglu Yang Nora Botten Robin Hodges Jeffrey Bair Tor P. Utheim Charles N. Serhan Darlene A. Dartt |
| author_facet | Menglu Yang Nora Botten Robin Hodges Jeffrey Bair Tor P. Utheim Charles N. Serhan Darlene A. Dartt |
| author_sort | Menglu Yang |
| collection | DOAJ |
| description | Resolvin (Rv) D2 and RvD1 are biosynthesized from docosahexaenoic acid (DHA) and promote resolution of inflammation in multiple organs and tissues, including the conjunctiva. Histamine is a mediator produced by mast cells in the conjunctiva during the allergic response. We determined the interaction of RvD2 with histamine and its receptor subtypes in cultured conjunctival goblet cells and compared them with RvD1 by measuring intracellular [Ca<sup>2+</sup>] and mucous secretion. Treatment with RvD2 significantly blocked the histamine-induced [Ca<sup>2+</sup>]<sub>i</sub> increase as well as secretion. RvD2 and RvD1 counter-regulate different histamine receptor subtypes. RvD2 inhibited the increase in [Ca<sup>2+</sup>]<sub>i</sub> induced by the activation of H1, H3, or H4 receptors, whereas RvD1 inhibited H1 and H3 receptors. RvD2 and RvD1 also activate distinct receptor-specific protein kinases to counter-regulate the histamine receptors, probably by phosphorylation. Thus, our data suggest that the counter-regulation of H receptor subtypes by RvD2 and RvD1 to inhibit mucin secretion are separately regulated. |
| first_indexed | 2024-03-10T03:39:22Z |
| format | Article |
| id | doaj.art-2bf9956ef8be4d2ba0ca1f393d4dcb06 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:39:22Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2bf9956ef8be4d2ba0ca1f393d4dcb062023-11-23T11:35:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0123114110.3390/ijms23010141Resolvin D2 and Resolvin D1 Differentially Activate Protein Kinases to Counter-Regulate Histamine-Induced [Ca<sup>2+</sup>]<sub>i</sub> Increase and Mucin Secretion in Conjunctival Goblet CellsMenglu Yang0Nora Botten1Robin Hodges2Jeffrey Bair3Tor P. Utheim4Charles N. Serhan5Darlene A. Dartt6Massachusetts Eye and Ear, Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USAMassachusetts Eye and Ear, Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USAMassachusetts Eye and Ear, Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USAMassachusetts Eye and Ear, Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USADepartment of Medical Biochemistry, Oslo University Hospital, 0316 Oslo, NorwayCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USAMassachusetts Eye and Ear, Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USAResolvin (Rv) D2 and RvD1 are biosynthesized from docosahexaenoic acid (DHA) and promote resolution of inflammation in multiple organs and tissues, including the conjunctiva. Histamine is a mediator produced by mast cells in the conjunctiva during the allergic response. We determined the interaction of RvD2 with histamine and its receptor subtypes in cultured conjunctival goblet cells and compared them with RvD1 by measuring intracellular [Ca<sup>2+</sup>] and mucous secretion. Treatment with RvD2 significantly blocked the histamine-induced [Ca<sup>2+</sup>]<sub>i</sub> increase as well as secretion. RvD2 and RvD1 counter-regulate different histamine receptor subtypes. RvD2 inhibited the increase in [Ca<sup>2+</sup>]<sub>i</sub> induced by the activation of H1, H3, or H4 receptors, whereas RvD1 inhibited H1 and H3 receptors. RvD2 and RvD1 also activate distinct receptor-specific protein kinases to counter-regulate the histamine receptors, probably by phosphorylation. Thus, our data suggest that the counter-regulation of H receptor subtypes by RvD2 and RvD1 to inhibit mucin secretion are separately regulated.https://www.mdpi.com/1422-0067/23/1/141ocular allergyconjunctivitishistamineSPMsRvD1RvD2 |
| spellingShingle | Menglu Yang Nora Botten Robin Hodges Jeffrey Bair Tor P. Utheim Charles N. Serhan Darlene A. Dartt Resolvin D2 and Resolvin D1 Differentially Activate Protein Kinases to Counter-Regulate Histamine-Induced [Ca<sup>2+</sup>]<sub>i</sub> Increase and Mucin Secretion in Conjunctival Goblet Cells International Journal of Molecular Sciences ocular allergy conjunctivitis histamine SPMs RvD1 RvD2 |
| title | Resolvin D2 and Resolvin D1 Differentially Activate Protein Kinases to Counter-Regulate Histamine-Induced [Ca<sup>2+</sup>]<sub>i</sub> Increase and Mucin Secretion in Conjunctival Goblet Cells |
| title_full | Resolvin D2 and Resolvin D1 Differentially Activate Protein Kinases to Counter-Regulate Histamine-Induced [Ca<sup>2+</sup>]<sub>i</sub> Increase and Mucin Secretion in Conjunctival Goblet Cells |
| title_fullStr | Resolvin D2 and Resolvin D1 Differentially Activate Protein Kinases to Counter-Regulate Histamine-Induced [Ca<sup>2+</sup>]<sub>i</sub> Increase and Mucin Secretion in Conjunctival Goblet Cells |
| title_full_unstemmed | Resolvin D2 and Resolvin D1 Differentially Activate Protein Kinases to Counter-Regulate Histamine-Induced [Ca<sup>2+</sup>]<sub>i</sub> Increase and Mucin Secretion in Conjunctival Goblet Cells |
| title_short | Resolvin D2 and Resolvin D1 Differentially Activate Protein Kinases to Counter-Regulate Histamine-Induced [Ca<sup>2+</sup>]<sub>i</sub> Increase and Mucin Secretion in Conjunctival Goblet Cells |
| title_sort | resolvin d2 and resolvin d1 differentially activate protein kinases to counter regulate histamine induced ca sup 2 sup sub i sub increase and mucin secretion in conjunctival goblet cells |
| topic | ocular allergy conjunctivitis histamine SPMs RvD1 RvD2 |
| url | https://www.mdpi.com/1422-0067/23/1/141 |
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