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Our previous <jats:italic>in vitro<\/jats:italic> studies indicate that RvD1 activation of ALX\/FPR2 resolves cytokine-mediated inflammatory responses in mammalian cells. However, the impact of ALX\/FPR2 activation on salivary gland function <jats:italic>in vivo<\/jats:italic> is unknown. The objective of this study was to determine whether submandibular glands (SMG) from <jats:italic>ALX<\/jats:italic>\/<jats:italic>FPR2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice display enhanced inflammatory responses to lipopolysaccharides (LPS) stimulation. For these studies, C57BL\/6 and <jats:italic>ALX\/FPR2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice at age 8-12-week-old were treated with LPS by <jats:italic>i.p<\/jats:italic> for 24\u2009h. Salivary gland structure and function were analyzed by histopathological assessment, saliva flow rate, quantitative PCR, Western blot analyses and immunofluorescence. Our results showed the following events in the <jats:italic>ALX\/FPR2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice treated with LPS: a) upregulated inflammatory cytokines and decreased M3R (Muscarinic Acetylcholine receptor M3) and AQP5 (Aquaporin 5) protein expression, b) decreased saliva secretion, c) increased apoptosis, d) alteration of tight junction and neuronal damage. Overall, our data suggest that the loss of ALX\/FPR2 results in unresolved acute inflammation and SMG dysfunction (xerostomia) in response to LPS that is similar to human salivary gland dysfunction induced by bacterial infection.<\/jats:p>","DOI":"10.1038\/srep24244","type":"journal-article","created":{"date-parts":[[2016,4,11]],"date-time":"2016-04-11T11:08:57Z","timestamp":1460372937000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["ALX\/FPR2 Modulates Anti-Inflammatory Responses in Mouse Submandibular Gland"],"prefix":"10.1038","volume":"6","author":[{"given":"Ching-Shuen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinshen","family":"Wee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieh-Hsiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Melvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga J.","family":"Baker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,4,11]]},"reference":[{"key":"BFsrep24244_CR1","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/S0030-6665(05)70173-0","volume":"32","author":"SJ McQuone","year":"1999","unstructured":"McQuone, S. 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