Basic–alimentary tractToll-Like Receptor 2 Controls Mucosal Inflammation by Regulating Epithelial Barrier Function
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Reagents and Antibodies
Synthetic lipopeptide Pam3Cys-SKKKKx3HCl (Pam3CysSK4 [PCSK]; Lots #E08/02, L08, L08/02) was obtained from EMC Microcollections GmbH (Tübingen, Germany) and prepared as previously described.21 Purified lipopolysaccharide (LPS) from Escherichia coli (R515) was obtained from Alexis Biochemicals (Grünberg, Germany). LY294002 was from Cell Signaling (Beverly, MA) and wortmannin from Calbiochem (Schwalbach, Germany). Monoclonal antibodies (mAbs) to CD45, pan-cytokeratin, phospho-JNK, phospho-cJun,
TLR2-induced PI3K-Akt Limits Immune Responsiveness and Promotes IEC Survival
The PI3K/Akt-pathway controls cell survival, which plays a critical role in maintaining barrier homeostasis. We therefore first investigated the functional role of the PI3K/Akt-pathway in TLR2-mediated signaling via MyD88 in IEC. Stimulation of 2 different IEC lines (differentiated: Caco-2; nondifferentiated: IEC-6 [data not shown]) with TLR2 ligands (synthetic PCSK, PGN) resulted in significant phosphorylation of Akt and activation of downstream p70S6K and ribosomal protein S6 in a time- and
Discussion
TLRs are involved in recognition and response to gram-negative and gram-positive bacterial cell wall components and play a key role in innate immunity.4 Individual TLRs interact with different combinations of adaptor proteins and functionally activate NFκB as central transcription factor, driving TLR-specific immune responses of defense in the intestinal epithelium,5, 16 yet the molecular functions of TLRs in the intestinal mucosa are not well understood.3 Here we characterize a novel
References (55)
- et al.
Characteristics of intestinal dendritic cells in inflammatory bowel diseases
Gastroenterology
(2005) - et al.
Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components
Immunity
(1999) - et al.
Intestinal epithelial TOLLerance versus inTOLLerance of commensals
Mol Immunol
(2005) - et al.
Mechanisms of cross hyporesponsiveness to Toll-like receptor bacterial ligands in intestinal epithelial cells
Gastroenterology
(2004) - et al.
Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis
Cell
(2004) - et al.
Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C
Gastroenterology
(2004) - et al.
Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice
Gastroenterology
(2002) Chitinase 3-like-1 exacerbates intestinal inflammation by enhancing bacterial adhesion and invasion in colonic epithelial cells
Gastroenterology
(2006)- et al.
Involvement of interleukin-1 in the development of ulcerative colitis induced by dextran sulfate sodium in mice
Cytokine
(1998) - et al.
PI3K: downstream AKTion blocks apoptosis
Cell
(1997)
Activate NF-kappa B or die?
Curr Biol
IL-6 Protects enterocytes from hypoxia-induced apoptosis by induction of bcl-2 mRNA and reduction of fas mRNA
Biochem Biophys Res Commun
Cox-2 is regulated by Toll-like receptor-4 (TLR4) signaling: Role in proliferation and apoptosis in the intestine
Gastroenterology
Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis
Gastroenterology
CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: a possible role in ulcerative colitis
Gastroenterology
CpG motifs of bacterial DNA essentially contribute to the perpetuation of chronic intestinal inflammation
Gastroenterology
Role of Toll-like receptors in spontaneous commensal-dependent colitis
Immunity
Inflammatory bowel disease
N Engl J Med
Molecular analysis of commensal host-microbial relationships in the intestine
Science
Bacterial interactions with cells of the intestinal mucosa: Toll-like receptors and NOD2
Gut
Innate immune recognition
Annu Rev Immunol
Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors
J Immunol
Synthetic lipopeptide analogs of bacterial lipoprotein are potent polyclonal activators for murine B lymphocytes
J Immunol
The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors
Proc Natl Acad Sci U S A
Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway
Nat Immunol
Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4
Nature
NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses
Nat Immunol
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Epithelial regulation of microbiota-immune cell dynamics
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Supported by DFG grants Ca226/4-1, Ca226/5-1, Ca226/4-2 (E.C.); IFORES award (E.C.); and NIH grants DK60049, DK43351, and DK41557 (D.K.P.).