{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:09:03Z","timestamp":1791922143866,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006706","name":"Tampereen Tuberkuloosis\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006706","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glucocorticoids are widely used in the treatment of allergic and inflammatory diseases. Glucocorticoids have a widespread action on gene expression resulting in their pharmacological actions and also an array of adverse effects which limit their clinical use. It remains, however, to be studied which target gene effects are essential for the anti\u2010allergic activity of glucocorticoids. Mitogen\u2010activated protein kinase phosphatase\u20101 (MKP\u20101) inhibits proinflammatory signalling by suppressing the activity of mitogen activated protein kinase (MAP kinase) pathways. MKP\u20101 is one of the anti\u2010inflammatory genes whose expression is enhanced by glucocorticoids. In the present study, we aimed to investigate the role of MKP\u20101 in the therapeutic effects of the glucocorticoid dexamethasone in acute allergic reaction. The effects of dexamethasone were studied in wild\u2010type and MKP\u20101 deficient mice. The mice were first sensitized to ovalbumin, and the allergic reaction was then induced by a subcutaneous ovalbumin injection in the hind paw. Inflammatory edema was quantified with plethysmometer and expression of inflammatory factors was measured by quantitative reverse transcription polymerase chain reaction (RT\u2010PCR). Dexamethasone reduced the ovalbumin\u2010induced paw edema at 1.5, 3 and 6\u00a0h time points in wild\u2010type mice by 70%, 95% and 89%, respectively. The effect was largely abolished in MKP\u20101 deficient mice. Furthermore, dexamethasone significantly attenuated the expression of ovalbumin\u2010induced inflammatory factors cyclooxygenase\u20102 (COX\u20102); inducible nitric oxide synthase (iNOS); interleukins (IL) 1\u03b2, 6 and 13; C\u2010C motif chemokine 11 (CCL\u201011); tumour necrosis factor (TNF) and thymic stromal lymphopoietin (TSLP) in wild\u2010type mice by more than 40%. In contrast, in MKP\u20101 deficient mice dexamethasone had no effect or even enhanced the expression of these inflammatory factors. The results suggest that dexamethasone alleviates allergic inflammation through an MKP\u20101\u2010dependent mechanism. The results also demonstrate MKP\u20101 as an important conveyor of the favourable glucocorticoid effects in ovalbumin\u2010induced type I allergic reaction. Together with previous findings, the present study supports the concept of MKP\u20101 enhancing compounds as potential novel anti\u2010inflammatory and anti\u2010allergic drugs.<\/jats:p>","DOI":"10.1111\/bcpt.13995","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T05:30:02Z","timestamp":1709616602000},"page":"686-694","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The glucocorticoid dexamethasone alleviates allergic inflammation through a mitogen\u2010activated protein kinase phosphatase\u20101\u2010dependent mechanism in mice"],"prefix":"10.1111","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9732-7138","authenticated-orcid":false,"given":"Tiina","family":"Lehtola","sequence":"first","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology Tampere University and Tampere University Hospital  Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Nummenmaa","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology Tampere University and Tampere University Hospital  Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riina","family":"Nieminen","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology Tampere University and Tampere University Hospital  Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"H\u00e4m\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology Tampere University and Tampere University Hospital  Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-1291","authenticated-orcid":false,"given":"Katriina","family":"Vuolteenaho","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology Tampere University and Tampere University Hospital  Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8577-0316","authenticated-orcid":false,"given":"Eeva","family":"Moilanen","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology Tampere University and Tampere University Hospital  Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737167.2020.1819793"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.117157"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2016_62"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01446"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073880"},{"issue":"5","key":"e_1_2_7_7_1","first-page":"925","article-title":"Disruption of the erp\/mkp\u20101 gene does not affect mouse development: normal MAP kinase activity in ERP\/MKP\u20101\u2010deficient fibroblasts","volume":"13","author":"Dorfman K","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000494932"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13944"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.037309"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.22.7802\u20107811.2002"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060336"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623312447551"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102567.2010.03313.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.8.5312"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6408"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.7108"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/09622935020138000"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.11.006"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R117.777318"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.11.4743\u20104756.2004"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.101747"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.171975"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.275370"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032\u2010008\u20109039\u20101"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.13995","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T09:04:03Z","timestamp":1713258243000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.13995"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,4]]},"references-count":24,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/bcpt.13995"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.13995","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,4]]},"assertion":[{"value":"2023-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}