scholarly journals Resolvin D1 Increases Mucin Secretion in Cultured Rat Conjunctival Goblet Cells via Multiple Signaling Pathways

2017 ◽  
Vol 58 (11) ◽  
pp. 4530 ◽  
Author(s):  
Marit Lippestad ◽  
Robin R. Hodges ◽  
Tor P. Utheim ◽  
Charles N. Serhan ◽  
Darlene A. Dartt
Keyword(s):  
Signaling Pathways ◽  
Goblet Cells ◽  
Resolvin D1 ◽  
Mucin Secretion ◽  
Multiple Signaling ◽  
Conjunctival Goblet Cells

scholarly journals Resolvin D2 and Resolvin D1 Differentially Activate Protein Kinases to Counter-Regulate Histamine-Induced [Ca2+]i Increase and Mucin Secretion in Conjunctival Goblet Cells

2021 ◽  
Vol 23 (1) ◽  
pp. 141
Author(s):  
Menglu Yang ◽  
Nora Botten ◽  
Robin Hodges ◽  
Jeffrey Bair ◽  
Tor P. Utheim ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Goblet Cells ◽  
Histamine Receptor ◽  
Specific Protein ◽  
Receptor Subtypes ◽  
Resolvin D1 ◽  
Mucin Secretion ◽  
Multiple Organs ◽  
H3 Receptors ◽  
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 of RvD2 with histamine and its receptor subtypes in cultured conjunctival goblet cells and compared them with RvD1 by measuring intracellular [Ca2+] and mucous secretion. Treatment with RvD2 significantly blocked the histamine-induced [Ca2+]i increase as well as secretion. RvD2 and RvD1 counter-regulate different histamine receptor subtypes. RvD2 inhibited the increase in [Ca2+]i 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.

scholarly journals Signaling pathways activated by resolvin E1 to stimulate mucin secretion and increase intracellular Ca 2+ in cultured rat conjunctival goblet cells

2018 ◽  
Vol 173 ◽  
pp. 64-72 ◽  
Author(s):  
Marit Lippestad ◽  
Robin R. Hodges ◽  
Tor P. Utheim ◽  
Charles N. Serhan ◽  
Darlene A. Dartt
Keyword(s):  
Signaling Pathways ◽  
Goblet Cells ◽  
Mucin Secretion ◽  
Intracellular Ca ◽  
Conjunctival Goblet Cells

scholarly journals RvE1 uses the LTB4 receptor BLT1 to increase [Ca2+]i and stimulate mucin secretion in cultured rat and human conjunctival goblet cells

2020 ◽  
Vol 18 (3) ◽  
pp. 470-482 ◽  
Author(s):  
Menglu Yang ◽  
Marit Lippestad ◽  
Robin R. Hodges ◽  
Haakon K. Fjærvoll ◽  
Ketil A. Fjærvoll ◽  
...  
Keyword(s):  
Goblet Cells ◽  
Mucin Secretion ◽  
Conjunctival Goblet Cells ◽  
Ltb4 Receptor

scholarly journals Resolvin E1 Reduces Leukotriene B4–Induced Intracellular Calcium Increase and Mucin Secretion in Rat Conjunctival Goblet Cells

2020 ◽  
Vol 190 (9) ◽  
pp. 1823-1832
Author(s):  
Menglu Yang ◽  
Jeffrey A. Bair ◽  
Robin R. Hodges ◽  
Charles N. Serhan ◽  
Darlene A. Dartt
Keyword(s):  
Intracellular Calcium ◽  
Goblet Cells ◽  
Leukotriene B4 ◽  
Mucin Secretion ◽  
Conjunctival Goblet Cells

scholarly journals Activation of the EGF Receptor by Histamine Receptor Subtypes Stimulates Mucin Secretion in Conjunctival Goblet Cells

2018 ◽  
Vol 59 (8) ◽  
pp. 3543 ◽  
Author(s):  
Min He ◽  
Marit Lippestad ◽  
Dayu Li ◽  
Robin R. Hodges ◽  
Tor P. Utheim ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Goblet Cells ◽  
Histamine Receptor ◽  
Receptor Subtypes ◽  
Mucin Secretion ◽  
Conjunctival Goblet Cells

scholarly journals Resolvins D3, D4, and D5 activate selective signaling pathways to increase intracellular [Ca 2+ ] in rat conjunctival goblet cells

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Jeffrey Bair ◽  
Robin Hodges ◽  
Morton Magno ◽  
Menglu Yang ◽  
Tor Utheim ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Goblet Cells ◽  
Intracellular Ca ◽  
Conjunctival Goblet Cells

scholarly journals Effect of Histamine on Ca2+-Dependent Signaling Pathways in Rat Conjunctival Goblet Cells

2012 ◽  
Vol 53 (11) ◽  
pp. 6928 ◽  
Author(s):  
Dayu Li ◽  
Richard B. Carozza ◽  
Marie A. Shatos ◽  
Robin R. Hodges ◽  
Darlene A. Dartt
Keyword(s):  
Signaling Pathways ◽  
Goblet Cells ◽  
Conjunctival Goblet Cells

scholarly journals Pro-Resolving Mediator Annexin A1 Regulates Intracellular Ca2+ and Mucin Secretion in Cultured Goblet Cells Suggesting a New Use in Inflammatory Conjunctival Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Anne V. Lyngstadaas ◽  
Markus V. Olsen ◽  
Jeffrey A. Bair ◽  
Robin R. Hodges ◽  
Tor P. Utheim ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Ocular Surface ◽  
Tear Film ◽  
Goblet Cells ◽  
Optimal Level ◽  
Annexin A1 ◽  
Mucin Secretion ◽  
Intracellular Ca ◽  
Dependent Protein ◽  
Conjunctival Goblet Cells

The amount of mucin secreted by conjunctival goblet cells is regulated to ensure the optimal level for protection of the ocular surface. Under physiological conditions lipid specialized pro-resolving mediators (SPM) are essential for maintaining tissue homeostasis including the conjunctiva. The protein Annexin A1 (AnxA1) can act as an SPM. We used cultured rat conjunctival goblet cells to determine if AnxA1 stimulates an increase in intracellular [Ca2+] ([Ca2+]i) and mucin secretion and to identify the signaling pathways. The increase in [Ca2+]i was determined using fura2/AM and mucin secretion was measured using an enzyme-linked lectin assay. AnxA1 stimulated an increase in [Ca2+]i and mucin secretion that was blocked by the cell-permeant Ca2+ chelator BAPTA/AM and the ALX/FPR2 receptor inhibitor BOC2. AnxA1 increased [Ca2+]i to a similar extent as the SPMs lipoxin A4 and Resolvin (Rv) D1 and histamine. The AnxA1 increase in [Ca2+]i and mucin secretion were inhibited by blocking the phospholipase C (PLC) pathway including PLC, the IP3 receptor, the Ca2+/ATPase that causes the intracellular Ca2+ stores to empty, and blockade of Ca2+ influx. Inhibition of protein kinase C (PKC) and Ca2+/calmodulin-dependent protein kinase also decreased the AnxA1-stimulated increase in [Ca2+]i and mucin secretion. In contrast inhibitors of ERK 1/2, phospholipase A2 (PLA2), and phospholipase D (PLD) did not alter AnxA1-stimulated increase in [Ca2+]i, but did inhibit mucin secretion. Activation of protein kinase A did not decrease either the AnxA1-stimulated rise in [Ca2+]i or secretion. We conclude that in health, AnxA1 contributes to the mucin layer of the tear film and ocular surface homeostasis by activating the PLC signaling pathway to increase [Ca2+]i and stimulate mucin secretion and ERK1/2, PLA2, and PLD to stimulate mucin secretion from conjunctival goblet cells.

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