{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:51:01Z","timestamp":1791589861411,"version":"4.3.4"},"reference-count":77,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Inflammatory bowel disease (IBD) patients display genetic polymorphisms in toll\u2010like receptor 4 (TLR4) genes, contributing to dysregulate enteric nervous system (ENS) circuits with increased levels of 5\u2010HT and alteration of the neuroimmune crosstalk. In this study, we investigated the impact of TLR4 signalling on mouse ENS dysfunction caused by dextran sulphate sodium (DSS)\u2010induced ileitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Male C57BL\/6J (wild\u2010type [WT]) and TLR4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice (10\u2009\u00b1\u20092\u2009weeks old) received 2% DSS in drinking water for 5\u2009days and then were switched to 3\u2010day regular drinking water. Histological analysis and proinflammatory cytokine mRNA levels were assessed in ileal samples. Gut motility was evaluated by changes in transit of a fluorescent\u2010labelled marker and isometric neuromuscular responses of ileal full\u2010thickness segments to receptor and non\u2010receptor\u2010mediated stimuli. Alterations in ENS architecture were assessed by confocal immunohistochemistry in longitudinal muscle\u2013myenteric plexus whole\u2010mount preparations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      In WT mice, DSS treatment caused delayed gastrointestinal transit, ileal myenteric neurodegeneration, reactive gliosis and release of proinflammatory cytokines. Enhanced cholinergic and tachykinergic excitatory tone, increased inducible nitric oxide synthase (iNOS)\u2010mediated relaxation, and changes in 5\u2010HT\n                      <jats:sub>2A<\/jats:sub>\n                      and 5\u2010HT\n                      <jats:sub>3<\/jats:sub>\n                      receptor\u2010mediated responses were observed during ileitis in WT mice. TLR4 deficiency reversed most of the functional and morphological abnormalities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Our results demonstrate that TLR4 activity influences the severity of ileitis, neuroglial plasticity, gut motility, and nitrergic and 5\u2010HTergic neurotransmissions. The neuroimmune interaction between TLR4 and 5\u2010HT observed in our study appears to be a potential pharmacological target to treat ENS dysfunction implicated in IBD onset\/progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.17439","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T18:44:06Z","timestamp":1737571446000},"page":"1803-1822","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Toll\u2010like receptor 4 deficiency ameliorates experimental ileitis and enteric neuropathy: Involvement of nitrergic and 5\u2010hydroxytryptaminergic neurotransmission"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4813-2259","authenticated-orcid":false,"given":"Sofia","family":"Faggin","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7099-4475","authenticated-orcid":false,"given":"Silvia","family":"Cerantola","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Caputi","sequence":"additional","affiliation":[{"name":"Poultry Production and Product Safety Research Unit, Agricultural Research Service United States Department of Agriculture  Fayetteville Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Tietto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padua  Padua Italy"},{"name":"School of Specialization in Clinical Pharmacology and Toxicology University of Ferrara  Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Stocco","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Padua  Padua Italy"},{"name":"Department of Women's and Children's Health University of Padua  Padua Italy"},{"name":"Department of Surgery, Oncology and Gastroenterology University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5027-880X","authenticated-orcid":false,"given":"Annalisa","family":"Bosi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ponti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Bertazzo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2335-6897","authenticated-orcid":false,"given":"Veronica","family":"Macchi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Porzionato","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3187-2894","authenticated-orcid":false,"given":"Edoardo V.","family":"Savarino","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3760-3441","authenticated-orcid":false,"given":"Cristina","family":"Giaroni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0825-7965","authenticated-orcid":false,"given":"Maria Cecilia","family":"Giron","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.4291\/wjgp.v2.i5.72"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16177"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16178"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.06.034"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0212856"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/1178646920928984"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.08.047"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2015.03.018"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0261-4"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-1012-5"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0394632015599707"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00350"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13965"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9050465"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040838"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120562"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126803"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2009.01346.x"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i10.1261"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14226"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2016.04.012"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-022-00611-w"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.03.023"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.07.003"},{"issue":"5","key":"e_1_2_12_29_1","first-page":"463","article-title":"Dextran sulfate sodium induces pan\u2010gastroenteritis in rodents: Implications for studies of colitis","volume":"63","author":"Elsheikh W.","year":"2012","journal-title":"Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-305005"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12619"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.09.008"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00328.2004"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2012.02.004"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232415632"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abi6442"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03812-y"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2005.02979.x"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1018849405922"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2003.11.004"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.11.017"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-37"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.94548"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169303"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11111791"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2023.137315"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14163"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2013.03.006"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14036"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25518"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0016-5085(00)70141-7"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjw162"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075426"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1540\/jsmr.43.43"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.11027"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.182"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1089\/sur.2009.053"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2022.102183"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2024.02.017"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1993.265.1.G156"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12292"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00423-7"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.563bw.x"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12664-020-01114-y"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703747"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13482"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-021-00443-1"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-065186"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00452.2009"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00052.2013"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu10060685"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2016.2486"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.727664"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izad312"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.766590"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1174655"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.17439","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T09:03:27Z","timestamp":1748336607000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.17439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,22]]},"references-count":77,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/bph.17439"],"URL":"https:\/\/doi.org\/10.1111\/bph.17439","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,22]]},"assertion":[{"value":"2024-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}