Cellular differentiation-induced attenuation of LPS response in HT-29 cells is related to the down-regulation of TLR4 expression

Lee, Sang Kil; Kim, Tae Il; Kim, Yun Kyung; Choi, Chang Hwan; Yang, Kyung Min; Chae, Boah; Kim, Won Ho

doi:10.1016/j.bbrc.2005.09.071

Cited by 49 publications

(25 citation statements)

References 44 publications

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“…We showed that IL-8 is dramatically increased (12-fold, P Ͻ 0.001) after HT-29 monolayers were treated for 6 h with LPS (Fig. 4), which corresponds with data shown by others (33). Inhibition of the PI3K pathway with LY294002 significantly decreased (30%, P Ͻ 0.05) LPS-induced IL-8 expression (Fig.…”

Section: Effect Of Pi3k On Il-8 Expressionsupporting

confidence: 88%

Tumor Suppressor Foxo3a Is Involved in the Regulation of Lipopolysaccharide-Induced Interleukin-8 in Intestinal HT-29 Cells

et al. 2008

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Section: Effect Of Pi3k On Il-8 Expressionsupporting

confidence: 88%

Tumor Suppressor Foxo3a Is Involved in the Regulation of Lipopolysaccharide-Induced Interleukin-8 in Intestinal HT-29 Cells

et al. 2008

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“…4A, right panel, shows that concomitant IL-4 priming partly reversed the up-regulatory effects IFN-␥ on TLR4 protein expression in IECs (4,19). Taken together, these data demonstrated that Th2 cytokine-mediated down-regulation of TLR4 mRNA expression in resting and Th1 cytokine-primed IECs led to a significant reduction in TLR4 protein expression.…”

Section: Diminished Tlr4 Protein Expression Reflects Down-regulated Tmentioning

confidence: 67%

“…HT29 cells have been reported to respond to all major TLR ligands, including the TLR5 ligand flagellin (22). Moreover, as noted above, recent studies also used HT29 cells to show increased LPS responsiveness after IFN-␥ priming (4,18,19).…”

Section: Th2 Cytokine-primed Iecs Show Functionally Impaired Tlr Signmentioning

confidence: 99%

“…Recent studies associated the mucosal Th1 cytokine profile in patients with Crohn's disease with enhanced intestinal TLR expression and signaling (16,17). Recent in vitro findings demonstrating that the key Th1 cytokine IFN-␥ promoted TLR4/MD-2-mediated signaling in model IECs (4,18,19), leading to increased IL-8 secretion upon stimulation with the specific TLR4 ligand LPS, underscored the important role of proinflammatory Th1 cytokines in the development and maintenance of chronic intestinal inflammation.…”

Section: Th2 Cytokines Down-regulate Tlr Expression and Function In Hmentioning

confidence: 99%

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Th2 Cytokines Down-Regulate TLR Expression and Function in Human Intestinal Epithelial Cells

Müller

Takato

Rosenberg

et al. 2006

The Journal of Immunology

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TLRs serve important immune and nonimmune functions in human intestinal epithelial cells (IECs). Proinflammatory Th1 cytokines have been shown to promote TLR expression and function in IECs, but the effect of key Th2 cytokines (IL-4, IL-5, IL-13) on TLR signaling in IECs has not been elucidated so far. We stimulated human model IECs with Th2 cytokines and examined TLR mRNA and protein expression by Northern blotting, RT-PCR, real-time RT-PCR, Western blotting, and flow cytometry. TLR function was determined by I-κBα phosphorylation assays, ELISA for IL-8 secretion after stimulation with TLR ligands and flow cytometry for LPS uptake. IL-4 and IL-13 significantly decreased TLR3 and TLR4 mRNA and protein expression including the requisite TLR4 coreceptor MD-2. TLR4/MD-2-mediated LPS uptake and TLR ligand-induced I-κBα phosphorylation and IL-8 secretion were significantly diminished in Th2 cytokine-primed IECs. The down-regulatory effect of Th2 cytokines on TLR expression and function in IECs also counteracted enhanced TLR signaling induced by stimulation with the hallmark Th1 cytokine IFN-γ. In summary, Th2 cytokines appear to dampen TLR expression and function in resting and Th1 cytokine-primed human IECs. Diminished TLR function in IECs under the influence of Th2 cytokines may protect the host from excessive TLR signaling, but likely also impairs the host intestinal innate immune defense and increases IEC susceptibility to chronic inflammation in response to the intestinal microenvironment. Taken together, our data underscore the important role of Th2 cytokines in balancing TLR signaling in human IECs.

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“…In addition, it has been reported that LPS induces the IL-8 secretion through TLR4 in HT-29 cells [17]. Therefore, we first evaluated the expression of TLR4 and CD14 in anti-67LR-treated cells and control cells (Isotype-treated cells).…”

Section: Resultsmentioning

confidence: 99%

Epigallocatechin-3-Gallate Regulates Anti-Inflammatory Action Through 67-kDa Laminin Receptor-Mediated Tollip Signaling Induction in Lipopolysaccharide-Stimulated Human Intestinal Epithelial Cells

Byun

Kim

Sung

et al. 2018

Cell Physiol Biochem

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Background/Aims: Inflammatory bowel disease (IBD) is a condition that involves chronic inflammation in all or part of the digestive tract. Often painful and debilitating, IBD can lead to life-threatening complications and increase the risk for colon cancer. In this study, we investigated the epigallocatechin-3-gallate (EGCG) mediated anti-inflammation response in lipopolysaccharide (LPS)-stimulated human colorectal cells through the negative regulator of Toll-like receptor (TLR) signaling. Methods: human intestinal epithelial cells (HT-29) were used in all experiments. Cell cytotoxicity and nitric oxide (NO) were evaluated by WST-1 and the Griess reagent. Western blot analysis and ELISA were used to determine inflammatory mediators and 67-kDa laminin receptor (67LR)-mediated Tollip signaling pathways. Results: Treatment of EGCG and LPS did not affect the cytotoxicity in HT-29 cells. LPS treatment dose-dependently increased the pro-inflammatory cytokine, such as interleukin (IL)-8, whereas EGCG significantly reduced the LPS-stimulated IL-8 production. Additionally, EGCG treatment markedly increased the Toll-interacting protein (Tollip) expression, which negatively regulates the TLR signaling in a dose and time-dependent manner. In particular, in the result from an RNA interference-mediated assay, our finding showed that silencing of Tollip resulted in abrogation of the inhibitory action of EGCG on LPS-induced production of pro-inflammatory mediators (inducible nitric oxide synthase-mediated NO/COX2, and IL-8) and activation of MAPKs and NF-κB signaling pathways. Interestingly, we also found that Tollip expression induced by EGCG could be modulated through 67LR expressed on the surface of HT-29 cells. Conclusions: Our novel finding indicates that 67LR and Tollip signaling activated by EGCG treatment is essential for inhibition of inflammation in human intestinal epithelial cells.

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Cellular differentiation-induced attenuation of LPS response in HT-29 cells is related to the down-regulation of TLR4 expression

Cited by 49 publications

References 44 publications

Tumor Suppressor Foxo3a Is Involved in the Regulation of Lipopolysaccharide-Induced Interleukin-8 in Intestinal HT-29 Cells

Tumor Suppressor Foxo3a Is Involved in the Regulation of Lipopolysaccharide-Induced Interleukin-8 in Intestinal HT-29 Cells

Th2 Cytokines Down-Regulate TLR Expression and Function in Human Intestinal Epithelial Cells

Epigallocatechin-3-Gallate Regulates Anti-Inflammatory Action Through 67-kDa Laminin Receptor-Mediated Tollip Signaling Induction in Lipopolysaccharide-Stimulated Human Intestinal Epithelial Cells

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