Mucin depleted foci, colonic preneoplastic lesions lacking Muc2, show up-regulation of Tlr2 but not bacterial infiltration.

Mucin depleted foci (MDF) are precancerous lesions of the colon in carcinogen-treated rodents and humans at high risk. Since MDF show signs of inflammation we hypothesized that the defective mucous production would expose them to the risk of being penetrated by intestinal bacteria, which can be sens...

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Autores principales:	Angelo Pietro Femia, Alexander Swidsinski, Piero Dolara, Maddalena Salvadori, Amedeo Amedei, Giovanna Caderni
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8a7127c75b004407aff62e5977678994
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spelling	oai:doaj.org-article:8a7127c75b004407aff62e59776789942021-11-18T07:30:50ZMucin depleted foci, colonic preneoplastic lesions lacking Muc2, show up-regulation of Tlr2 but not bacterial infiltration.1932-620310.1371/journal.pone.0029918https://doaj.org/article/8a7127c75b004407aff62e59776789942012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22242189/?tool=EBIhttps://doaj.org/toc/1932-6203Mucin depleted foci (MDF) are precancerous lesions of the colon in carcinogen-treated rodents and humans at high risk. Since MDF show signs of inflammation we hypothesized that the defective mucous production would expose them to the risk of being penetrated by intestinal bacteria, which can be sensed by Toll-like receptors (Tlrs) and activate inflammatory pathways. To verify this hypothesis we tested the expression of 84 genes coding for Tlrs and associated pathways using RT-qPCR in MDF (n = 7) from 1,2-dimethylhydrazine (DMH)-treated rats. Among the 84 tested genes, 26 were differentially expressed in MDF with 5 genes significantly up-regulated and 21 down-regulated when compared to the normal mucosa. Tlr2, as well as other downstream genes (Map4k4, Hspd1, Irak1, Ube2n), was significantly up-regulated. Among the genes regulating the NFkB pathway, only Map4k4 was significantly up-regulated, while 19 genes were not varied and 6 were down-regulated. Tlr2 protein was weakly expressed both in normal mucosa and MDF. To determine whether inflammation observed in MDF could be caused by bacteria contacting or infiltrating crypts, we performed fluorescence in situ hybridization (FISH) experiments with a rRNA universal bacterial probe. None of the 21 MDF tested, showed bacteria inside the crypts, while among the colonic tumors (n = 15), only one had very few bacteria on the surface and on the surrounding normal mucosa. In conclusion, the up-regulation of Tlr2 in MDF, suggests a link between this receptor and carcinogenesis, possibly related to a defective barrier function of these lesions. The data of FISH experiments do not support the hypothesis that inflammation in MDF and tumors is stimulated by bacterial infiltration.Angelo Pietro FemiaAlexander SwidsinskiPiero DolaraMaddalena SalvadoriAmedeo AmedeiGiovanna CaderniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29918 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angelo Pietro Femia Alexander Swidsinski Piero Dolara Maddalena Salvadori Amedeo Amedei Giovanna Caderni Mucin depleted foci, colonic preneoplastic lesions lacking Muc2, show up-regulation of Tlr2 but not bacterial infiltration.
description	Mucin depleted foci (MDF) are precancerous lesions of the colon in carcinogen-treated rodents and humans at high risk. Since MDF show signs of inflammation we hypothesized that the defective mucous production would expose them to the risk of being penetrated by intestinal bacteria, which can be sensed by Toll-like receptors (Tlrs) and activate inflammatory pathways. To verify this hypothesis we tested the expression of 84 genes coding for Tlrs and associated pathways using RT-qPCR in MDF (n = 7) from 1,2-dimethylhydrazine (DMH)-treated rats. Among the 84 tested genes, 26 were differentially expressed in MDF with 5 genes significantly up-regulated and 21 down-regulated when compared to the normal mucosa. Tlr2, as well as other downstream genes (Map4k4, Hspd1, Irak1, Ube2n), was significantly up-regulated. Among the genes regulating the NFkB pathway, only Map4k4 was significantly up-regulated, while 19 genes were not varied and 6 were down-regulated. Tlr2 protein was weakly expressed both in normal mucosa and MDF. To determine whether inflammation observed in MDF could be caused by bacteria contacting or infiltrating crypts, we performed fluorescence in situ hybridization (FISH) experiments with a rRNA universal bacterial probe. None of the 21 MDF tested, showed bacteria inside the crypts, while among the colonic tumors (n = 15), only one had very few bacteria on the surface and on the surrounding normal mucosa. In conclusion, the up-regulation of Tlr2 in MDF, suggests a link between this receptor and carcinogenesis, possibly related to a defective barrier function of these lesions. The data of FISH experiments do not support the hypothesis that inflammation in MDF and tumors is stimulated by bacterial infiltration.
format	article
author	Angelo Pietro Femia Alexander Swidsinski Piero Dolara Maddalena Salvadori Amedeo Amedei Giovanna Caderni
author_facet	Angelo Pietro Femia Alexander Swidsinski Piero Dolara Maddalena Salvadori Amedeo Amedei Giovanna Caderni
author_sort	Angelo Pietro Femia
title	Mucin depleted foci, colonic preneoplastic lesions lacking Muc2, show up-regulation of Tlr2 but not bacterial infiltration.
title_short	Mucin depleted foci, colonic preneoplastic lesions lacking Muc2, show up-regulation of Tlr2 but not bacterial infiltration.
title_full	Mucin depleted foci, colonic preneoplastic lesions lacking Muc2, show up-regulation of Tlr2 but not bacterial infiltration.
title_fullStr	Mucin depleted foci, colonic preneoplastic lesions lacking Muc2, show up-regulation of Tlr2 but not bacterial infiltration.
title_full_unstemmed	Mucin depleted foci, colonic preneoplastic lesions lacking Muc2, show up-regulation of Tlr2 but not bacterial infiltration.
title_sort	mucin depleted foci, colonic preneoplastic lesions lacking muc2, show up-regulation of tlr2 but not bacterial infiltration.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8a7127c75b004407aff62e5977678994
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Mucin depleted foci, colonic preneoplastic lesions lacking Muc2, show up-regulation of Tlr2 but not bacterial infiltration.

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