Resolvin E1 Reduces Leukotriene B4–Induced Intracellular Calcium Increase and Mucin Secretion in Rat Conjunctival Goblet Cells
Autor: | Charles N. Serhan, Menglu Yang, Jeffrey Bair, Robin R. Hodges, Darlene A. Dartt |
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Rok vydání: | 2020 |
Předmět: |
Male
Leukotriene B4 Inflammation Article Calcium in biology Pathology and Forensic Medicine Proinflammatory cytokine Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Secretion Receptor Kinase Mucins hemic and immune systems respiratory system Molecular biology biological factors Rats respiratory tract diseases Eicosapentaenoic Acid chemistry 030221 ophthalmology & optometry Calcium lipids (amino acids peptides and proteins) Goblet Cells medicine.symptom Conjunctiva Intracellular 030215 immunology |
Zdroj: | Am J Pathol |
ISSN: | 0002-9440 |
Popis: | Leukotriene B4 (LTB4) is a major proinflammatory mediator important in host defense, whereas resolvins (Rvs) are produced during the resolution phase of inflammation. The authors determined the actions of both RvE1 and RvD1 on LTB4–induced responses of goblet cells cultured from rat conjunctiva. The responses measured were an increase in the intracellular [Ca(2+)] ([Ca(2+)](i)) and high–molecular-weight glycoprotein secretion. Treatment with RvE1 or RvD1 for 30 minutes significantly blocked the LTB4–induced [Ca(2+)](i) increase. The actions of RvE1 on LTB4–induced [Ca(2+)](i) increase were reversed by siRNA for the RvE1 receptor, and the actions of RvD1 were reversed by an RvD1 receptor inhibitor. The RvE1 and RvD1 block of LTB4-stimulated increase in [Ca(2+)](i) was also reversed by an inhibitory peptide to β-adrenergic receptor kinase. LTB4 and block of the LTB4–stimulated increase in [Ca(2+)](i) by RvE1 and RvD1 were partially mediated by the depletion of intracellular Ca(2+) stores. RvE1, but not RvD1, counterregulated the LTB4–induced high–molecular-weight glycoprotein secretion. Thus, both RvE1 and RvD1 receptors directly inhibit LTB4 by phosphorylating the LTB4 receptor using β adrenergic receptor kinase. RvE1 receptor counterregulates the LTB4–induced increase in [Ca(2+)](i) and secretion, whereas RvD1 receptor only counterregulates LTB4–induced [Ca(2+)](i) increase. |
Databáze: | OpenAIRE |
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