Gamma Interferon Augments the Intracellular Pathway for Lipopolysaccharide (LPS) Recognition in Human Intestinal Epithelial Cells through Coordinated Up-Regulation of LPS Uptake and Expression of the Intracellular Toll-Like Receptor 4-MD-2 Complex

Suzuki, Manabu; Hisamatsu, Tadakazu; Podolsky, Daniel K.

doi:10.1128/iai.71.6.3503-3511.2003

Cited by 206 publications

(178 citation statements)

References 45 publications

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“…In addition, we show that both NF-B and AP-1 transactivation are required for the full expression of ␤-defensin-2 in IEC. We and others (10,16) have shown that expression of TLRs is increased in response to Th1 cytokines in IBD mucosa and may also be upregulated by infection with pathogens. Our findings provide a mechanistic explanation for the up-regulation of ␤-defensin-2 in the setting of increased bacterial signaling.…”

Section: Discussionmentioning

confidence: 99%

“…We and others have previously shown that T84 and Caco-2 cells are poorly responsive to LPS and PGN due to low expression of the TLR4 and TLR2 complexes (10,14,15). By contrast, Suzuki et al (10) have described LPS responsiveness in SW480 cells, a colon cancer cell line. We hypothesized that PAMPs stimulate the expression of the antimicrobial peptide ␤-defensin-2 in IEC.…”

Section: Pamps Stimulate Expression Of ␤-Defensin-2 In Iecmentioning

confidence: 99%

“…We have previously shown that IEC are poorly responsive to Gram-positive and Gram-negative PAMPs, because they express low levels of TLR2, TLR6, TLR4, and its accessory molecule MD-2 (14,15). In response to cytokine stimulation, expression of TLR4 and MD-2 is increased (10,16), suggesting that TLR expression is increased in the setting of infections or idiopathic IBD (17).…”

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confidence: 99%

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β-Defensin-2 Expression Is Regulated by TLR Signaling in Intestinal Epithelial Cells

Vora¹,

Youdim²,

Thomas³

et al. 2004

The Journal of Immunology

322

225

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The intestinal epithelium serves as a barrier to the intestinal flora. In response to pathogens, intestinal epithelial cells (IEC) secrete proinflammatory cytokines. To aid in defense against bacteria, IEC also secrete antimicrobial peptides, termed defensins. The aim of our studies was to understand the role of TLR signaling in regulation of β-defensin expression by IEC. The effect of LPS and peptidoglycan on β-defensin-2 expression was examined in IEC lines constitutively or transgenically expressing TLRs. Regulation of β-defensin-2 was assessed using promoter-reporter constructs of the human β-defensin-2 gene. LPS and peptidoglycan stimulated β-defensin-2 promoter activation in a TLR4- and TLR2-dependent manner, respectively. A mutation in the NF-κB or AP-1 site within the β-defensin-2 promoter abrogated this response. In addition, inhibition of Jun kinase prevents up-regulation of β-defensin-2 protein expression in response to LPS. IEC respond to pathogen-associated molecular patterns with expression of the antimicrobial peptide β-defensin-2. This mechanism may protect the intestinal epithelium from pathogen invasion and from potential invaders among the commensal flora.

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Section: Discussionmentioning

confidence: 99%

Section: Pamps Stimulate Expression Of ␤-Defensin-2 In Iecmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

β-Defensin-2 Expression Is Regulated by TLR Signaling in Intestinal Epithelial Cells

Vora¹,

Youdim²,

Thomas³

et al. 2004

The Journal of Immunology

322

225

View full text Add to dashboard Cite

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“…Dissimilar to plasma membrane localized TLR4 in macrophages, TLR4 has been shown to be localized predominately in the Golgi apparatus in enterocytes (174), and TLR4 activation in enterocytes has been shown to require intracellular recognition of LPS in the Golgi apparatus and recruitment of IRAK-1 and MyD88 to the Golgi apparatus (195). Furthermore, colonic HT-29 and colo205 cells express TLR4 predominately in cytoplasmic fractions and are hyporesponsive to LPS in basal states (89). Intracellular TLR redistribution has been suggested as a mechanism for flagellin tolerance, as prolonged flagellin exposure resulted in redistribution of TLR5 to an intracellular location in T84 colonocytes.…”

Section: Peaceful Coexistence: Mechanisms Allowing Epithelial Cells Tmentioning

confidence: 99%

No Longer an Innocent Bystander: Epithelial Toll-Like Receptor Signaling in the Development of Mucosal Inflammation

Gribar

Richardson

Sodhi

et al. 2008

Mol Med

142

109

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Diseases of mucosal inflammation represent important causes of morbidity and mortality, and have led to intense research efforts to understand the factors that lead to their development. It is well accepted that a breakdown of the normally impermeant epithelial barrier of the intestine, the lung, and the kidney is associated with the development of inflammatory disease in these organs, yet significant controversy exists as to how this breakdown actually occurs, and how such a breakdown may lead to inflammation. In this regard, much work has focused upon the role of the epithelium as an "innocent bystander," a target of a leukocyte-mediated inflammatory cascade that leads to its destruction in the mucosal inflammatory process. However, recent evidence from a variety of laboratories indicates that the epithelium is not merely a passive component in the steps that lead to mucosal inflammation, but is a central participant in the process. In addressing this controversy, we and others have determined that epithelial cells express Toll-like receptors (TLRs) of the innate immune system, and that activation of TLRs by endogenous and exogenous ligands may play a central role in determining the balance between a state of "mucosal homeostasis," as is required for optimal organ function, and "mucosal injury," leading to mucosal inflammation and barrier breakdown. In particular, activation of TLRs within intestinal epithelial cells leads to the development of cellular injury and impairment in mucosal repair in the pathogenesis of intestinal inflammation, while activation of TLRs in the lung and kidney may participate in the development of pneumonitis and nephritis respectively. Recent work in support of these concepts is extensively reviewed, while essential areas of further study that are required to determine the significance of epithelial TLR signaling during states of health and disease are outlined.

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“…The expression of the macrophage tumouricidal capacity is dependent on their activation status. Various agents, including the interferon-γ (IFN-γ), lipopolysaccharide (LPS) and lectins are known to activate the macrophages (Suzuki et al, 2003;Schorey and Lawrence, 2008). Once activated, macrophages can inhibit the growth of tumor cells and microorganisms (Nascimento et al, 2002), mainly due to the increases in the production of NO, H 2 O 2 and cytokines.…”

Section: Discussionmentioning

confidence: 99%

The effect of phosphoethanolamine intake on mortality and macrophage activity in mice with solid ehrlich tumors

Arruda

Corrêa

Venturini

et al. 2011

Braz. arch. biol. technol.

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show abstract

Gamma Interferon Augments the Intracellular Pathway for Lipopolysaccharide (LPS) Recognition in Human Intestinal Epithelial Cells through Coordinated Up-Regulation of LPS Uptake and Expression of the Intracellular Toll-Like Receptor 4-MD-2 Complex

Cited by 206 publications

References 45 publications

β-Defensin-2 Expression Is Regulated by TLR Signaling in Intestinal Epithelial Cells

β-Defensin-2 Expression Is Regulated by TLR Signaling in Intestinal Epithelial Cells

No Longer an Innocent Bystander: Epithelial Toll-Like Receptor Signaling in the Development of Mucosal Inflammation

The effect of phosphoethanolamine intake on mortality and macrophage activity in mice with solid ehrlich tumors

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