Human intestinal epithelial cells secrete interleukin-1 receptor antagonist and interleukin-8 but not interleukin-1 or interleukin-6

Daig, R; Rogler, Gerhard; Aschenbrenner, E; Vogl, Daniela; Falk, Werner; Groß, Volker; Schölmerich, Jürgen; Andus, Tilo

doi:10.1136/gut.46.3.350

Cited by 94 publications

(64 citation statements)

References 31 publications

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“…However, these studies did not explore the functional consequences of TLR2 signaling in IEC. Our findings demonstrate that IEC are poorly responsive to a variety of TLR2 ligands with respect to proinflammatory gene expression and IL-8 secretion, two outcomes relevant to acute and chronic intestinal inflammation (92)(93)(94). Although the response to certain TLR2 ligands could be restored by transgenic expression of TLR2 and TLR6, IEC remained poorly responsive to bacterial lipopeptide suggesting that, in addition to TLR2 and TLR1, other coreceptors or signaling molecules may be functionally deficient as well.…”

Section: Discussionmentioning

confidence: 75%

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

Melmed¹,

Thomas²,

Lee³

et al. 2003

The Journal of Immunology

396

281

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Intestinal epithelial cells (IEC) interact with a high density of Gram-positive bacteria and are active participants in mucosal immune responses. Recognition of Gram-positive organisms by Toll-like receptor (TLR)2 induces proinflammatory gene expression by diverse cells. We hypothesized that IEC are unresponsive to Gram-positive pathogen-associated molecular patterns and sought to characterize the functional responses of IEC to TLR2-specific ligands. Human colonic epithelial cells isolated by laser capture microscopy and IEC lines (Caco-2, T84, HT-29) were analyzed for expression of TLR2, TLR6, TLR1, and Toll inhibitory protein (Tollip) mRNA by RT-PCR and quantitative real-time PCR. Response to Gram-positive bacterial ligands was measured by NF-κB reporter gene activation and IL-8 secretion. TLR2 protein expression was analyzed by immunofluorescence and flow cytometry. Colonic epithelial cells and lamina propria cells from both uninflamed and inflamed tissue demonstrate low expression of TLR2 mRNA compared with THP-1 monocytes. IECs were unresponsive to TLR2 ligands including the staphylococcal-derived Ags phenol soluble modulin, peptidoglycan, and lipotechoic acid and the mycobacterial-derived Ag soluble tuberculosis factor. Transgenic expression of TLR2 and TLR6 restored responsiveness to phenol soluble modulin and peptidoglycan in IEC. In addition to low levels of TLR2 protein expression, IEC also express high levels of the inhibitory molecule Tollip. We conclude that IEC are broadly unresponsive to TLR2 ligands secondary to deficient expression of TLR2 and TLR6. The relative absence of TLR2 protein expression by IEC and high level of Tollip expression may be important in preventing chronic proinflammatory cytokine secretion in response to commensal Gram-positive bacteria in the gut.

show abstract

Section: Discussionmentioning

confidence: 75%

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

Melmed¹,

Thomas²,

Lee³

et al. 2003

The Journal of Immunology

396

281

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“…IL-1Ra specifically inhibits IL-1 activities by binding to IL-1 receptors, but does not display agonist activity [5,12,16,[19][20][21][22]. In the intestinal mucosa, epithelial cells and lamina propria mononuclear cells are the major sources of IL-1Ra [23]. An imbalance between the production of IL-1 and IL-1Ra has been described in freshly isolated intestinal mucosal cells [24] and in colonic mucosal biopsies obtained from inflamed intestinal tissue of IBD patients [25].…”

Section: Introductionmentioning

confidence: 99%

Imbalance between interleukin-1 agonists and antagonists: relationship to severity of inflammatory bowel disease

Ludwiczek

Vannier

Borggraefe

et al. 2004

Clinical and Experimental Immunology

126

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SUMMARYInterleukin (IL)-1 is a key mediator in the pathogenesis of inflammatory bowel disease (IBD). Naturally occurring IL-1 modulators include IL-1 receptor antagonist (IL-1Ra), IL-1 soluble receptor Type I (IL1sRI), IL-1sRII and IL-1 receptor accessory protein (AcP). Systemic and mucosal levels of IL-1 soluble receptors remain unknown in IBD. Plasma or colonic tissues were obtained from 185 consecutive unselected patients with Crohn's disease (CD) or ulcerative colitis (UC) and from 52 control subjects. Plasma and colonic explant culture supernatants were assessed for IL-1 a , IL-1 b , IL-1Ra, IL-1sRI and IL-1sRII. Plasma IL-1Ra levels were higher in UC (+93%) than in healthy subjects. IL-1 a and IL-1 b were not detected. IL-1sRII levels were marginally lower in CD ( -10%) and UC ( -9%), whereas IL1sRI levels were elevated in CD (+28%) only. Plasma IL-1sRI levels correlated positively ( P < 0·01) with Crohn's disease activity index ( r = 0·53), C-reactive protein ( r = 0·46) and a 1-acid glycoprotein ( r = 0·42). In colonic explant cultures, IL-1 a and IL-1Ra levels were elevated in non-lesional (+233% and +185% respectively) and lesional CD (+353% and +1069%), lesional UC (+604% and +1138%), but not in non-lesional UC. IL-1 b was elevated in lesional UC (+152%) and CD (+128%). In contrast, IL-1sRII levels were elevated in non-lesional CD (+65%), but remained unchanged in lesional CD, nonlesional and lesional UC. IL-1sRI levels did not differ between patient and control groups. These results indicate that (i) the proinflammatory moiety IL-1sRI is a systemic marker of inflammation and activity in CD and (ii) local shedding of the functional antagonist IL-1sRII may dampen colonic inflammation in CD, but not in UC.

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“…Periephitelial region of the small bowel and subephitelial dome of the Peyer's plaques are some of the places that they are located. In these localizations, the first defense mechanism is formed against the pathogens found in the colon lumen [16,17]. In CC cases, considering the immune response system's systematic response in which cellular unit plays a leading role, presence of inflammatory cells found somewhere (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…In CC cases, considering the immune response system's systematic response in which cellular unit plays a leading role, presence of inflammatory cells found somewhere (e.g. gastric and/or duodenal mucosa) other than the location where the disease is primarily localized must be checked out and their presence in such locations will support the diagnosis of the disease [16,17]. Recently, it has been reported that MMA found in gastroduodenal mucosa by immunochemical methods supports the diagnosis of CD.…”

Section: Discussionmentioning

confidence: 99%

Role of Macrophage Microaggregation in the Diagnosis of Inflammatory Colitis

Altunoğlu¹,

Tuncer²,

Erten³

et al. 2014

Ann Clin Anal Med

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Human intestinal epithelial cells secrete interleukin-1 receptor antagonist and interleukin-8 but not interleukin-1 or interleukin-6

Cited by 94 publications

References 31 publications

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

Imbalance between interleukin-1 agonists and antagonists: relationship to severity of inflammatory bowel disease

Role of Macrophage Microaggregation in the Diagnosis of Inflammatory Colitis

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