PMID- 15499080
OWN - NLM
STAT- MEDLINE
DCOM- 20050316
LR  - 20201226
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 288
IP  - 3
DP  - 2005 Mar
TI  - Toll-like receptor-mediated responses of primary intestinal epithelial cells 
      during the development of colitis.
PG  - G514-24
AB  - The interleukin-2-deficient (IL-2(-/-)) mouse model of ulcerative colitis was 
      used to test the hypothesis that colonic epithelial cells (CEC) directly respond 
      to bacterial antigens and that alterations in Toll-like receptor (TLR)-mediated 
      signaling may occur during the development of colitis. TLR expression and 
      activation of TLR-mediated signaling pathways in primary CEC of healthy animals 
      was compared with CEC in IL-2(-/-) mice during the development of colitis. In 
      healthy animals, CEC expressed functional TLR, and in response to the TLR4 ligand 
      LPS, proliferated and secreted the cytokines IL-6 and monocyte chemoattractant 
      protein-1 (MCP-1). However, the TLR-responsiveness of CEC in IL-2(-/-) mice was 
      different with decreased TLR4 responsiveness and augmented TLR2 responses that 
      result in IL-6 and MCP-1 secretion. TLR signaling in CEC did not involve 
      NF-kappaB (p65) activation with the inhibitory p50 form of NF-kappaB 
      predominating in CEC in both the healthy and inflamed colon. Development of 
      colitis was, however, associated with the activation of MAPK family members and 
      upregulation of MyD88-independent signaling pathways characterized by increased 
      caspase-1 activity and IL-18 production. These findings identify changes in TLR 
      expression and signaling during the development of colitis that may contribute to 
      changes in the host response to bacterial antigens seen in colitis.
FAU - Singh, Joy Carmelina Indira
AU  - Singh JC
AD  - School of Biochemistry and Microbiology, The University of Leeds, Leeds, LS2 9JT, 
      UK.
FAU - Cruickshank, Sheena Margaret
AU  - Cruickshank SM
FAU - Newton, Darren James
AU  - Newton DJ
FAU - Wakenshaw, Louise
AU  - Wakenshaw L
FAU - Graham, Anne
AU  - Graham A
FAU - Lan, Jinggang
AU  - Lan J
FAU - Lodge, Jeremy Peter Alan
AU  - Lodge JP
FAU - Felsburg, Peter John
AU  - Felsburg PJ
FAU - Carding, Simon Richard
AU  - Carding SR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041021
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (DNA, Complementary)
RN  - 0 (Interleukin-18)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Antigens, Differentiation/physiology
MH  - Bacteria/metabolism
MH  - Blotting, Western
MH  - Caspase 1/metabolism
MH  - Cell Separation
MH  - Cells, Cultured
MH  - Colitis/*pathology
MH  - DNA, Complementary/biosynthesis/genetics
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epithelial Cells/*pathology
MH  - Flow Cytometry
MH  - Interleukin-18/biosynthesis
MH  - Intestines/*pathology
MH  - Membrane Glycoproteins/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88
MH  - RNA, Messenger/biosynthesis/isolation & purification
MH  - Receptors, Cell Surface/genetics/*physiology
MH  - Receptors, Immunologic/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/physiology
MH  - Toll-Like Receptor 2
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
MH  - Up-Regulation/physiology
EDAT- 2004/10/23 09:00
MHDA- 2005/03/17 09:00
CRDT- 2004/10/23 09:00
PHST- 2004/10/23 09:00 [pubmed]
PHST- 2005/03/17 09:00 [medline]
PHST- 2004/10/23 09:00 [entrez]
AID - 00377.2004 [pii]
AID - 10.1152/ajpgi.00377.2004 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2005 Mar;288(3):G514-24. doi: 
      10.1152/ajpgi.00377.2004. Epub 2004 Oct 21.