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dc.contributor.authorKurt-Jones, Evelyn A.
dc.contributor.authorCao, LuCheng
dc.contributor.authorSandor, Frantisek
dc.contributor.authorRogers, Arlin B.
dc.contributor.authorWhary, Mark T.
dc.contributor.authorNambiar, Prashant R.
dc.contributor.authorCerny, Anna M.
dc.contributor.authorBowen, Glennice N.
dc.contributor.authorYan, Jing
dc.contributor.authorTakaishi, Shigeo
dc.contributor.authorChi, Alfred L.
dc.contributor.authorReed, George W.
dc.contributor.authorHoughton, JeanMarie
dc.contributor.authorFox, James G.
dc.contributor.authorWang, Timothy C.
dc.date2022-08-11T08:10:03.000
dc.date.accessioned2022-08-23T16:53:22Z
dc.date.available2022-08-23T16:53:22Z
dc.date.issued2006-11-15
dc.date.submitted2008-07-15
dc.identifier.citationInfect Immun. 2007 Jan;75(1):471-80. Epub 2006 Nov 13. <a href="http://dx.doi.org/10.1128/IAI.02039-05">Link to article on publisher's site</a>
dc.identifier.issn0019-9567 (Print)
dc.identifier.doi10.1128/IAI.02039-05
dc.identifier.pmid17101660
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42260
dc.description.abstractTrefoil family factor 2 (TFF2), also known as spasmolytic peptide, is a low-molecular-weight protein that is upregulated in gastric tissues infected with Helicobacter or having other inflammatory conditions, but a precise function is yet to be elucidated. The role of TFF2 in the development of gastritis, colitis, and inflammatory cytokine responses was examined both in vivo and in vitro using wild-type and TFF2 knockout mice. TFF2 knockout and wild-type mice were infected with Helicobacter felis (H. felis) to induce gastritis. Colitis was induced in TFF2 knockout and wild-type mice by administering dextran sodium sulfate (DSS) in drinking water. Histopathology, clinical disease (colitis), and antibody levels (H. felis) were examined. TFF2 expression in tissues was determined by reverse transcriptase PCR, and the inflammatory and proliferative responses of TFF2-expressing macrophages and spleen cells were examined by cytokine enzyme-linked immunosorbent assay, thymidine incorporation, and gene array studies. TFF2 knockout mice have increased susceptibility to H. felis-induced gastritis, with enhanced gastric inflammation. They were also more susceptible to DSS-induced colitis, with prolonged colonic hemorrhage and persistent weight loss. Remarkably, TFF2 expression was not limited to the gastrointestinal tract, as suggested in previous studies, but was also present in macrophages and lymphocytes. The inflammatory and proliferative responses of these immune cell types were dysregulated in TFF2 knockout mice. TFF2-/- cells were hyperresponsive to interleukin 1 beta stimulation but showed normal responses to lipopolysaccharide, suggesting a specific role for TFF2 in interleukin 1 receptor but not Toll-like receptor 4 signaling via their Toll-interleukin 1 resistance domains. TFF2-/- lymphocytes also produced higher levels of interleukin 2 than wild-type cells. Thus, TFF2 was expressed in the gastrointestinal cells and in immune cells and was a negative regulator of gastrointestinal inflammation and immune cell cytokine responses. Our studies suggest that TFF2 not only controls gastrointestinal repair but also regulates mononuclear cell inflammatory responses.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17101660&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectAnimals
dc.subjectCytokines
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectGastric Mucosa
dc.subjectGastrointestinal Diseases
dc.subjectGene Expression
dc.subjectGene Expression Profiling
dc.subjectHelicobacter Infections
dc.subjectHelicobacter felis
dc.subjectInflammation
dc.subjectIntestines
dc.subjectLymphocytes
dc.subjectMacrophages
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMucins
dc.subjectMuscle Proteins
dc.subjectOligonucleotide Array Sequence Analysis
dc.subjectPeptides
dc.subjectReceptors, Interleukin-1
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectStomach
dc.subjectDigestive System Diseases
dc.subjectGenetics and Genomics
dc.subjectPreventive Medicine
dc.titleTrefoil family factor 2 is expressed in murine gastric and immune cells and controls both gastrointestinal inflammation and systemic immune responses
dc.typeJournal Article
dc.source.journaltitleInfection and immunity
dc.source.volume75
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1622&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/623
dc.identifier.contextkey549052
refterms.dateFOA2022-08-23T16:53:23Z
html.description.abstract<p>Trefoil family factor 2 (TFF2), also known as spasmolytic peptide, is a low-molecular-weight protein that is upregulated in gastric tissues infected with Helicobacter or having other inflammatory conditions, but a precise function is yet to be elucidated. The role of TFF2 in the development of gastritis, colitis, and inflammatory cytokine responses was examined both in vivo and in vitro using wild-type and TFF2 knockout mice. TFF2 knockout and wild-type mice were infected with Helicobacter felis (H. felis) to induce gastritis. Colitis was induced in TFF2 knockout and wild-type mice by administering dextran sodium sulfate (DSS) in drinking water. Histopathology, clinical disease (colitis), and antibody levels (H. felis) were examined. TFF2 expression in tissues was determined by reverse transcriptase PCR, and the inflammatory and proliferative responses of TFF2-expressing macrophages and spleen cells were examined by cytokine enzyme-linked immunosorbent assay, thymidine incorporation, and gene array studies. TFF2 knockout mice have increased susceptibility to H. felis-induced gastritis, with enhanced gastric inflammation. They were also more susceptible to DSS-induced colitis, with prolonged colonic hemorrhage and persistent weight loss. Remarkably, TFF2 expression was not limited to the gastrointestinal tract, as suggested in previous studies, but was also present in macrophages and lymphocytes. The inflammatory and proliferative responses of these immune cell types were dysregulated in TFF2 knockout mice. TFF2-/- cells were hyperresponsive to interleukin 1 beta stimulation but showed normal responses to lipopolysaccharide, suggesting a specific role for TFF2 in interleukin 1 receptor but not Toll-like receptor 4 signaling via their Toll-interleukin 1 resistance domains. TFF2-/- lymphocytes also produced higher levels of interleukin 2 than wild-type cells. Thus, TFF2 was expressed in the gastrointestinal cells and in immune cells and was a negative regulator of gastrointestinal inflammation and immune cell cytokine responses. Our studies suggest that TFF2 not only controls gastrointestinal repair but also regulates mononuclear cell inflammatory responses.</p>
dc.identifier.submissionpathoapubs/623
dc.contributor.departmentDivision of Digestive Diseases and Nutrition
dc.contributor.departmentDepartment of Medicine, Division of Preventive and Behavorial Medicine
dc.source.pages471-80


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