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Inflammation is initiated by the release of pro-inflammatory mediators and terminated by the biosynthesis of specialized pro-resolution mediators (SPMs). Herein, we determined the sex-based difference in the responses of CGCs to inflammatory stimuli or pro-resolving lipid SPMs and their interaction with sex hormones. GCs were cultured from pieces of human conjunctiva in RPMI media. CGCs were transferred 24\u00a0h before the start of experiments to phenol red-free and FBS-free media to minimize exogenous hormones. RT-PCR, immunofluorescence microscopy (IF), and Western Blot (WB) were performed to determine the presence of sex hormone receptors. Cellular response to pro-inflammatory stimuli or SPMs was studied by measuring the increase in intracellular [Ca<jats:sup>2+<\/jats:sup>] ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) using fura 2\/AM microscopy. Use of RT-PCR demonstrated estrogen receptor (ER) \u03b1 in 4\/5 males and 3\/3 females; ER\u03b2 in 2\/4 males and 2\/3 females; and androgen receptors (AR) in 3\/3 male and 3\/3 female CGCs. Positive immunoreactivity by IF and protein expression by WB was detected using antibodies for the ER\u03b1 and ER\u03b2 in 3\/3 males and 3\/3 females, while AR were only present in males. Significantly different Ca<jats:sup>2+<\/jats:sup> responses between sexes were found with carbachol only at 10<jats:sup>\u20133<\/jats:sup>\u00a0M, but not with histamine or leukotriene (LT) B<jats:sub>4<\/jats:sub> at any concentration used. Incubation with dihydrotestosterone (DHT), estrone (E1), or estradiol (E2) at 10<jats:sup>\u20137<\/jats:sup>\u00a0M for 30\u00a0min significantly inhibited the LTB<jats:sub>4<\/jats:sub>-stimulated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> increase in male and female CGCs. Incubation with DHT, E1, and E2 overnight significantly inhibited the LTB<jats:sub>4<\/jats:sub> response in females, while DHT and E2 significantly inhibited the LTB<jats:sub>4<\/jats:sub> response in males. The SPM lipoxin A<jats:sub>4<\/jats:sub> (LXA<jats:sub>4<\/jats:sub>) (10<jats:sup>\u20139<\/jats:sup>\u201310<jats:sup>\u22128<\/jats:sup>\u00a0M), but not the resolvins D1 or D2, induced an [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> increase that was significantly higher in males compared to females. We conclude that male and female CGCs showed differences in the expression of sex hormone receptors. Treatment with sex hormones altered pro-inflammatory mediator LTB<jats:sub>4<\/jats:sub>-induced response. Males compared to females have a higher response to the \u03c9-6-fatty acid derived SPM LXA<jats:sub>4<\/jats:sub>, indicating males may terminate inflammation in conjunctival goblet cells faster than females.<\/jats:p>","DOI":"10.1038\/s41598-022-20177-9","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T14:04:02Z","timestamp":1664460242000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sex-based differences in conjunctival goblet cell responses to pro-inflammatory and pro-resolving mediators"],"prefix":"10.1038","volume":"12","author":[{"given":"Menglu","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haakon K.","family":"Fj\u00e6rvoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketil A.","family":"Fj\u00e6rvoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas H.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor P.","family":"Utheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4627-8545","authenticated-orcid":false,"given":"Charles N.","family":"Serhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darlene A.","family":"Dartt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"20177_CR1","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1001\/archophthalmol.2009.103","volume":"127","author":"DA Schaumberg","year":"2009","unstructured":"Schaumberg, D. 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