Abstract
Mucin hypersecretion is an important component of the immune response to gastrointestinal nematode infection. Two discrete types of mucin proteins exist in the mouse intestine, secretory Muc2 and membrane-bound Muc3. We examined Muc2 and Muc3 expression in wild-type mice and mice lacking gamma interferon receptor (IFNγR−/−), tumor necrosis factor receptor 1 (TNFR1−/−) and interleukin 4 (IL4−/−) infected with Trichinella spiralis. Infected wild-type mice demonstrated significant goblet cell hyperplasia and increased mucin glycoprotein. In situ hybridization showed this was accompanied by increases in Muc2 and Muc3 mRNA. Total intestinal mucin protein and Muc2 and Muc3 mRNA levels were also significantly increased in cytokine-deficient mice. These data demonstrate the coordinated up-regulation of two types of mucin genes in response to T. spiralis infection and may form the basis of an innate mucosal response independent of IFN-γ, TNF, and IL-4.
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REFERENCES
Garside P, Grencis R, Mowat A: T lymphocyte dependent enteropathy in murine Trichinella spiralis infection.Parasite Immunol14:217–225,1992
Ishikawa N, Horii Y, Oinuma T, Suganuma T, Nawa Y: Goblet cell mucins as the selective barrier for the intestinal helminths: T-cell-independent alteration of goblet cell mucins by immunologically “damaged” Nippostrongylus worms and its signifi-cance on the challenge infection with homologous and heterologous parasites.Immunology81:480–486,1994
Chang S-Y, Dohrman AF, Basbaum CB, Ho SB, Toribara NW, Gum JR, Kim YS: Localization of mucin (MUC2 and MUC3) messenger RNA and peptide expression in human normal intestine and colon cancer.Gastroenterology107:28–36,1994
Ho SB, Niehans GA, Lyftogt C, Yan P-S, Cherwitz DL, Gum ET, Dahiya R, Kim YS:Heterogeneity of mucin gene expression in normal and neoplastic tissues.Cancer Res53:641–651, 1993
Ohmori H, Dohrman AF, Gallup M, Tsuda T, Kai H, Gum JR, Kim YS, Basbaum CB:Molecular cloning of the aminoterminal region of a rat MUC2 mucin gene homologue.J Biol Chem269:17833–17840,1994
Xu G, Huan L-J, Khatri IA, Wang D, Bennick A, Fahim REF, Forstner GG, Forstner JF: cDNA for the carboxyl-terminal region of a rat intestinal mucin-like peptide.J Biol Chem 267:5401–5407,1992
Shekels LL, Hunninghake DA, Tisdale AS, Gipson LK, Kieliszewski M, Kozak CA, Ho SB: Cloning and characterization of mouse intestinal MUC3 mucin: 39 sequence contains EGF-like domains.Biochem J 330:1301–1308,1998
Crawley SC, Gum JR, Hicks JW, Pratt WS, Aubert JP, Swallow DM, Kim YS:Genomic organization and structure of the 39 region of human MUC3: alternative splicing predicts membrane-bound and soluble forms of the mucin. BBRC263:728–736,1999
Lawerence C, Paterson J, Higgins L, MacDonald T, Kennedy M, Garside P: IL-4-regulated enteropathy in an intestinal nematode infection.Eur J Immunol 28:2672–2684,1998
Shamsuddin A, Phelps P, and Trump B: Human large intestinal epithelium: Light microscopy, histochemistry and ultrastructure. Hum Pathol13:790–795,1982
Lin J, Kawano H, Paparella MM, Ho SB: Improved RNA analysis for immediate autopsy of temporal bone soft tissue. Acta Otolaryngol.119:787–795,1999
Carter JH, Richmond RE, Carter HW, Potter CI, Daniel FB, DeAngelo AB: Quantitative image cytometry of hepatocytes expressing gamma-glutamyl transpeptidase and glutathione Stransferase in diethylnitrosamine-initiated rats treated with phenobarbital and/or phthalate esters.Journal of Histochemistry and Cytochemistry 40:1105–1115,1992
Temann UA, Prasad B, Gallup MW, Basbaum C, Ho SB, Flavell RA, Rankin JA: A novel role for murine IL-4 in vivo: Induction of MUC5AC gene expression and mucin hypersecretion. Am. J Cell Mol Biol16:471–478,1997
Cohn L, Homer RJ, Marinov A, Rankin J, Bottomly T: Induction of airway mucus production by T helper (Th2) cells: A critical role for interleukin 4 in cell recruitment but not mucus production.J Exp Med186:1737–1747,1997
Cohan V, Scott A, Dinarello C: Interleukin-1 is a mucus secretagogue.Cell Immunol136:425–434,1991
Arnold JW, Klimpel GR, Niesel DW:Tumor necrosis factor (TNF alpha) regulates intestinal mucous production during salmonellosis.Cell Immunol151:336–344,1993
Ishikawa N, Wakelin D, Mahida Y: Role of T helper 2 cells in intestinal goblet cell hyperplasia in mice infected with Trichinella spiralis.Gastroenterology 113:542–549,1997
Grunig G, Warnock M, Wakil A, Venkayya R, Brombacher F, Rennick D, Sheppard D, Mohrs M, Donaldson D, Locksley R, et al:Requirement for IL-13 independently of IL-4 in experimental asthma. Science282:2261–2263,1998
McKenzie G, Bancroft A, Grencis R, McKenzie A: A distinct role for interleukin-13 in Th2-cell-mediated immune responses. Curr Biol8:339–342,1998
Fischer B, Rochelle L, Voynow J, Akley N, Adler K: Tumor necrosis factor-alpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro. Am J Respir Cell Mol Biol 20:000, 1999
Branka JE, Vallette G, Jarry A, and Laboisse CL: Stimulation of mucin exocytosis from human epithelial cells by nitric oxide: Evidence for a cGMP-dependent and a cGMP-independent pathway. Biochem J 323:521–528, 1997
Lawrence CE, Paterson JCM, Wei X-Q, Liew F-Y, Garside P, Kennedy MW: Nitric oxide mediates intestinal pathology but not immune expulsion during Trichinella spiralis infection in mice.J Immunol2000 (in press)
Belley A, Keller K, Grove J, Chadee K: Interaction of LS174T human colon cancer cell mucins with Entamoeba histolytica: An in vitro model for colonic disease.Gastroenterology111:1484–1492,1996
Williams SJ, Munster DJ, Quin RJ, Gotley DC, McGuckin MA: The MUC3 gene encodes a transmembrane mucin and is alternatively spliced.BBRC 261:83–89,1999
Moniaux N, Nollet S, Porchet N, Degand P, Laine A, Aubert JP: Complete sequence of the human mucin MUC4: A putative cell membrane-associated mucin.Biochem J338:325–333,1999
Sheng Z, Wu K, Carraway K, Fregien N: Molecular cloning of the transmembrane component of the 13762 mammary adenocarcinoma sialomucin complex: A new member of the epidermal growth factor superfamily.J Biol Chem 267:16341–16346, 1992
Wu K, Fregien N, Carraway KL: Molecular cloning and sequencing of the mucin subunit of a heterodimeric, bifunctional cell surface glycoprotein complex of ascites rat mammary adenocarcinoma cell.J Biol Chem 269:11950–11955,1994
Rossi EA, McNeer RR, Price-Schiavi S, Van den Brande JMH, Komatsu M, Thompson JF, Carraway CAC, Fregien NL, Carraway KL: Sialomucin complex, a heterodimeric glycoprotein complex: expression as a soluble secretable form in lactating mammary gland and colon.J Biol Chem271:33476–33485, 1996
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Shekels, L.L., Anway, R.E., Lin, J. et al. Coordinated Muc2 and Muc3 Mucin Gene Expression in Trichinella spiralis Infection in Wild-Type and Cytokine-Deficient Mice. Dig Dis Sci 46, 1757–1764 (2001). https://doi.org/10.1023/A:1010622125040
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DOI: https://doi.org/10.1023/A:1010622125040