PMID- 22242189
OWN - NLM
STAT- MEDLINE
DCOM- 20120508
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 1
DP  - 2012
TI  - Mucin depleted foci, colonic preneoplastic lesions lacking Muc2, show 
      up-regulation of Tlr2 but not bacterial infiltration.
PG  - e29918
LID - 10.1371/journal.pone.0029918 [doi]
LID - e29918
AB  - 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.
FAU - Femia, Angelo Pietro
AU  - Femia AP
AD  - Department of Pharmacology, University of Florence, Florence, Italy.
FAU - Swidsinski, Alexander
AU  - Swidsinski A
FAU - Dolara, Piero
AU  - Dolara P
FAU - Salvadori, Maddalena
AU  - Salvadori M
FAU - Amedei, Amedeo
AU  - Amedei A
FAU - Caderni, Giovanna
AU  - Caderni G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120105
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Mucin-2)
RN  - 0 (Tlr2 protein, rat)
RN  - 0 (Toll-Like Receptor 2)
SB  - IM
MH  - Animals
MH  - Bacteria/*metabolism
MH  - Colon/metabolism/microbiology/pathology
MH  - Colonic Neoplasms/*genetics/*microbiology
MH  - Down-Regulation/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Mucin-2/*deficiency/metabolism
MH  - Precancerous Conditions/microbiology/*pathology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Signal Transduction/genetics
MH  - Toll-Like Receptor 2/*genetics/metabolism
MH  - Up-Regulation/*genetics
PMC - PMC3252347
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/01/14 06:00
MHDA- 2012/05/09 06:00
PMCR- 2012/01/05
CRDT- 2012/01/14 06:00
PHST- 2011/07/29 00:00 [received]
PHST- 2011/12/06 00:00 [accepted]
PHST- 2012/01/14 06:00 [entrez]
PHST- 2012/01/14 06:00 [pubmed]
PHST- 2012/05/09 06:00 [medline]
PHST- 2012/01/05 00:00 [pmc-release]
AID - PONE-D-11-14713 [pii]
AID - 10.1371/journal.pone.0029918 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(1):e29918. doi: 10.1371/journal.pone.0029918. Epub 2012 Jan 5.