{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:43:41Z","timestamp":1792457021667,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,23]],"date-time":"2019-04-23T00:00:00Z","timestamp":1555977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["RO1EY019470"],"award-info":[{"award-number":["RO1EY019470"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["RO1GM038765"],"award-info":[{"award-number":["RO1GM038765"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Under physiologic conditions, conjunctival goblet cells (CGCs) secrete mucins into the tear film to preserve ocular surface homeostasis. Specialized proresolving mediators (SPMs), like resolvins (Rvs), regulate secretion from CGCs and actively terminate inflammation. The purpose of this study was to determine if RvD2 stimulated mucin secretion and to investigate the cellular signaling components. Goblet cells were cultured from rat conjunctiva. Secretion was measured by an enzyme\u2010linked lectin assay, change in intracellular [Ca\n 2+<\/jats:sup>\n ] ([Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n ) using Fura\u20102, and cellular cAMP levels by ELISA. RvD2 (10\n \u221211<\/jats:sup>\n \u201310\n \u22128<\/jats:sup>\n M) stimulated secretion, increased cellular cAMP levels and the [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n . RvD2\u2010stimulated increase in [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n and secretion was blocked by Ca\n 2+<\/jats:sup>\n chelator 1,2\u2010bis(2\u2010aminophenoxy)ethane\u2010\n N, N, N\u2032, N\u2032<\/jats:italic>\n \u2010tetraacetic acid tetrakis and the PKA inhibitor\n N<\/jats:italic>\n \u2010[2\u2010(p\u2010bromocinnamylamino)ethyl]\u20105\u2010isoquinolinesulfonamide dihydrochloride but not by the cAMP exchange protein inhibitor \u03b1[2\u2010(3\u2010chlorophenyl)hydrazinylidene]\u20105\u2010(1,1\u2010dimethylethyl)\u2010b\u2010oxo\u20103\u2010isoxazolepropanenitrile. Forskolin, 3\u2010isobutyl\u20101\u2010methylxanthine, and 8\u2010bromo\u2010cAMP (8\u2010Br\u2010cAMP) increased [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n . Increasing cAMP with 8\u2010Br\u2010cAMP inhibited the increase in [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n stimulated by the cAMP\u2010independent agonist cholinergic agonist carbachol. In conclusion, RvD2 uses both cellular cAMP and [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n to stimulate glycoconjugate secretion from CGCs, but the interaction of cAMP and [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n is context dependent. Thus RvD2 likely assists in the maintenance of the mucous layer of the tear film to sustain ocular surface homeostasis and has potential as a novel treatment for dry eye disease.\u2014Botten, N., Hodges, R. R., Li, D., Bair, J. A., Shatos, M. A., Utheim, T. P., Serhan, C. N., Dartt, D. A. Resolvin D2 elevates cAMP to increase intracellular [Ca\n 2+<\/jats:sup>\n ] and stimulate secretion from conjunctival goblet cells. FASEB J. 33, 8468\u20138478 (2019).\n www.fasebj.org<\/jats:ext-link>\n <\/jats:p>","DOI":"10.1096\/fj.201802467r","type":"journal-article","created":{"date-parts":[[2019,4,23]],"date-time":"2019-04-23T18:42:22Z","timestamp":1556044942000},"page":"8468-8478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Resolvin D2 elevates cAMP to increase intracellular [Ca\n 2+<\/sup>\n ] and stimulate secretion from conjunctival goblet cells"],"prefix":"10.1096","volume":"33","author":[{"given":"Nora","family":"Botten","sequence":"first","affiliation":[{"name":"Schepens Eye Research Institute Massachusetts Eye and Ear Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Medical Biochemistry Oslo University Hospital Oslo Norway"},{"name":"Department of Plastic and Reconstructive Surgery Oslo University Hospital Oslo Norway"},{"name":"Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin R.","family":"Hodges","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute Massachusetts Eye and Ear Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayu","family":"Li","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute Massachusetts Eye and Ear Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Bair","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute Massachusetts Eye and Ear Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie A.","family":"Shatos","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute Massachusetts Eye and Ear Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor P.","family":"Utheim","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute Massachusetts Eye and Ear Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Medical Biochemistry Oslo University Hospital Oslo Norway"},{"name":"Department of Plastic and Reconstructive Surgery Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles N.","family":"Serhan","sequence":"additional","affiliation":[{"name":"Center for Experimental Therapeutics and Reperfusion Injury Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Anesthesiology Perioperative, and Pain Medicine Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darlene A.","family":"Dartt","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute Massachusetts Eye and Ear Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2013.7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e32830e6b04"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(03)31001-0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000098"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2017.08.002"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/89759"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020760"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000833"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2010.0019"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e31823f789e"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003456"},{"key":"e_1_2_8_13_1","first-page":"274","article-title":"Resolvin D1 promotes corneal epithelial wound healing and restoration of mechanical sensation in diabetic mice","volume":"24","author":"Zhang Z.","year":"2018","journal-title":"Mol. 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