Validation of LPS induced esophageal inflammation through TLR4 pathway in gastroesophageal reflux disease

Validation of LPS induced esophageal inflammation through TLR4 pathway in gastroesophageal reflux disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Validation of LPS induced esophageal inflammation through TLR4 pathway in gastroesophageal reflux disease Zhi-tong Li, Yi-min Guo, Li-dong Chen, Qi Liu, Ming Cheng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4762668/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective : Current researches have shown that patients with gastroesophageal reflux disease (GERD) may have esophageal microbial flora imbalance, in which Gram-negative bacteria become dominant and produce lipopolysaccharide (LPS), which can activate the Toll-like receptor 4 (TLR4) signaling pathway. Therefore, we want to validate LPS induces esophageal inflammation through TLR4 pathway in GERD. Methods : We constructed an external esophageal perfusion rat model and used normal saline, LPS and TAK-242 + LPS mixture to perfuse the middle and lower esophagus, respectively. We observed the change of esophageal tissue inner diameter, the pathological changes of the esophagus, the expression of inflammatory factors, and the content of related apoptotic proteins in different groups. Results : In LPS group, obvious inflammatory infiltration was observed. The TAK-242 + LPS group exhibited a milder inflammatory response than the LPS group. Compared with the control, the LPS group had increased inflammatory factor expression and apoptotic protein content, with lowered anti-apoptotic gene expression. TAK-242, as a TLR4 inhibitor in the TAK-242 + LPS group, effectively suppressed the LPS-stimulated inflammatory response. Conclusion : LPS exerted the powerful pro-inflammatory effect through TLR4 pathway in GERD, and TAK-242, a TLR4 inhibitor, significantly alleviated LPS-induced esophageal damage, suggesting its potential as a GERD therapy. Health sciences/Gastroenterology Health sciences/Gastroenterology/Gastrointestinal diseases Health sciences/Gastroenterology/Gastrointestinal diseases/Dysbiosis Health sciences/Gastroenterology/Gastrointestinal diseases/Oesophageal diseases lipopolysaccharide gastroesophageal reflux disease toll-like receptor 4 esophageal inflammation Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4762668","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":335486560,"identity":"3b7482a9-b0a9-4f01-bfc6-575b775f6470","order_by":0,"name":"Zhi-tong Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYBACxgbmhgOMDRJg9oOEihpitDCCtYD0MBs8OHOMOHtACKSFTfJhCzNhDcwzEhsP/txhUccv3X6tIrGBjYG/vTsBvx0zEhsOSJ6RkJCcc6bsRuIOGQaJM2c3ENZi2CYhYXAjJ+1G4hk2BgOJXCK0JEK1FCS2MROp5SBYS/oxBuK09DxsONjYJiE5c0YOs0TCmWM8BP1i2J58+OPPtjp+fon0hx9/VNTI8bf3EtAyIQHG5DEAk3iVg4A8/wEYk/0BQdWjYBSMglEwMgEATJRP6jsRtpgAAAAASUVORK5CYII=","orcid":"","institution":"Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"prefix":"","firstName":"Zhi-tong","middleName":"","lastName":"Li","suffix":""},{"id":335486563,"identity":"12a66070-9317-4bab-9c31-651e1607e2d9","order_by":1,"name":"Yi-min Guo","email":"","orcid":"","institution":"Department of Radiology, The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yi-min","middleName":"","lastName":"Guo","suffix":""},{"id":335486566,"identity":"eb80c7fc-759e-4c55-8e7c-a9033ec621bd","order_by":2,"name":"Li-dong Chen","email":"","orcid":"","institution":"Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Li-dong","middleName":"","lastName":"Chen","suffix":""},{"id":335486567,"identity":"f0dcdcb8-81f6-4c21-a7b8-4dc97f2a14cf","order_by":3,"name":"Qi Liu","email":"","orcid":"","institution":"Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Liu","suffix":""},{"id":335486569,"identity":"16d66e13-ec0b-44f2-a5a1-44833776c9ed","order_by":4,"name":"Ming Cheng","email":"","orcid":"","institution":"Department of Medical Information, The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Cheng","suffix":""}],"badges":[],"createdAt":"2024-07-18 12:36:35","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4762668/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4762668/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":64153957,"identity":"6908b238-bbf2-4f26-8f4d-3d87f8b94851","added_by":"auto","created_at":"2024-09-09 03:56:11","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":704908,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript7.25.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4762668/v1_covered_5262a544-b209-4f95-8cf3-422670e42baa.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Validation of LPS induced esophageal inflammation through TLR4 pathway in gastroesophageal reflux disease","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"lipopolysaccharide, gastroesophageal reflux disease, toll-like receptor 4, esophageal inflammation","lastPublishedDoi":"10.21203/rs.3.rs-4762668/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4762668/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: Current researches have shown that patients with gastroesophageal reflux disease (GERD) may have esophageal microbial flora imbalance, in which Gram-negative bacteria become dominant and produce lipopolysaccharide (LPS), which can activate the Toll-like receptor 4 (TLR4) signaling pathway. Therefore, we want to validate LPS induces esophageal inflammation through TLR4 pathway in GERD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: We constructed an external esophageal perfusion rat model and used normal saline, LPS and TAK-242 + LPS mixture to perfuse the middle and lower esophagus, respectively. We observed the change of esophageal tissue inner diameter, the pathological changes of the esophagus, the expression of inflammatory factors, and the content of related apoptotic proteins in different groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: In LPS group, obvious inflammatory infiltration was observed. The TAK-242 + LPS group exhibited a milder inflammatory response than the LPS group. Compared with the control, the LPS group had increased inflammatory factor expression and apoptotic protein content, with lowered anti-apoptotic gene expression. TAK-242, as a TLR4 inhibitor in the TAK-242 + LPS group, effectively suppressed the LPS-stimulated inflammatory response.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: LPS exerted the powerful pro-inflammatory effect through TLR4 pathway in GERD, and TAK-242, a TLR4 inhibitor, significantly alleviated LPS-induced esophageal damage, suggesting its potential as a GERD therapy.\u003c/p\u003e","manuscriptTitle":"Validation of LPS induced esophageal inflammation through TLR4 pathway in gastroesophageal reflux disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-21 05:01:29","doi":"10.21203/rs.3.rs-4762668/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cd2d1918-46c1-4481-bdb9-c56e03117a5b","owner":[],"postedDate":"August 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":35532685,"name":"Health sciences/Gastroenterology"},{"id":35532686,"name":"Health sciences/Gastroenterology/Gastrointestinal diseases"},{"id":35532687,"name":"Health sciences/Gastroenterology/Gastrointestinal diseases/Dysbiosis"},{"id":35532688,"name":"Health sciences/Gastroenterology/Gastrointestinal diseases/Oesophageal diseases"}],"tags":[],"updatedAt":"2024-09-09T03:48:03+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-21 05:01:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4762668","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4762668","identity":"rs-4762668","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}