{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:19:24Z","timestamp":1790173164854,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K20237"],"award-info":[{"award-number":["16K20237"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K16881"],"award-info":[{"award-number":["18K16881"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The chromosomal region 17q21 harbors the human orosomucoid\u2010like 3 (<jats:italic>ORMDL3<\/jats:italic>) gene and has been linked to asthma and other inflammatory diseases. ORMDL3 is involved in the unfolded protein response (UPR), lipid metabolism, and inflammatory reactions. We investigated the effects of ORMDL3 overexpression in RBL\u20102H3 cells to determine the contribution of ORMDL3 to inflammatory disease development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated ORMDL3 stably overexpressing RBL\u20102H3 cells to assess degranulation, transcriptional upregulation of interleukin\u20104 (IL\u20104), tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), monocyte chemoattractant protein\u20101 (MCP\u20101), and mitogen\u2010activated protein kinase (MAPK) phosphorylation via Fc\u03b5RI. In addition, we examined the effects of ORMDL3 overexpression on thapsigargin (TG)\u2010mediated proinflammatory cytokine transcription and UPR by monitoring MAPK, protein kinase\u2010like endoplasmic reticulum kinase (PERK), and inositol\u2010requiring enzyme 1 (IRE1) phosphorylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overexpression of ORMDL3 enhanced IL\u20104, TNF\u2010\u03b1, and MCP\u20101 expression after Fc\u03b5RI cross\u2010linking, whereas the sphingosine\u20101\u2010phosphate (S1P) agonist FTY720 suppressed this enhancement. There was no significant difference in degranulation and MAPK phosphorylation via Fc\u03b5RI\u2010mediated activation between vector\u2010transfected and ORMDL3\u2010overexpressing cells. ORMDL3 overexpression accelerated TG\u2010mediated PERK phosphorylation, while MAPK phosphorylation and proinflammatory cytokine expression showed no significant changes in ORMDL3\u2010overexpressing cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that ORMDL3 plays an important role in regulating proinflammatory cytokine expression via the S1P pathway and selectively affects the UPR pathway in mast cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.489","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T15:53:50Z","timestamp":1626710030000},"page":"1394-1405","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["ORMDL3 overexpression facilitates Fc\u03b5RI\u2010mediated transcription of proinflammatory cytokines and thapsigargin\u2010mediated PERK phosphorylation in RBL\u20102H3 cells"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7358-7784","authenticated-orcid":false,"given":"Kazuhiro","family":"Ogi","sequence":"first","affiliation":[{"name":"Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences University of Fukui  Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Takabayashi","sequence":"additional","affiliation":[{"name":"Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences University of Fukui  Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Tomita","sequence":"additional","affiliation":[{"name":"Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences University of Fukui  Fukui 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