Endotoxin Stimulates Interleukin-6 Production in Intestinal Epithelial Cells

Meyer, Tory A.; Noguchi, Yoshifumi; Ogle, Cora K.; Tiao, Greg; Wang, Jing Jing; Fischer, Josef E.; Hasselgren, Per Olof

doi:10.1001/archsurg.1994.01420360080010

Cited by 54 publications

(24 citation statements)

References 20 publications

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“…In recent studies from our laboratory, mucosal production of IL-6 was increased in response to sepsis and endotoxemia (27,49), and cultured enterocytes produced IL-6 after treatment with endotoxin (26) or IL-1␤ (35). In other experiments, we found that induction of the heat shock response resulted in augmented IL-6 production in mucosa of endotoxemic mice (48) and in IL-1␤-stimulated cultured human enterocytes (33).…”

mentioning

confidence: 48%

Proteasome inhibitors induce heat shock response and increase IL-6 expression in human intestinal epithelial cells

Pritts

Hungness²,

Hershko

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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In previous studies, the heat shock response, induced by hyperthermia or sodium arsenite, increased interleukin (IL)-6 production in intestinal mucosa and cultured human enterocytes. A novel way to induce the heat shock response, documented in other cell types, is treatment with proteasome inhibitors. It is not known if proteasome inhibition induces heat shock in enterocytes or influences IL-6 production. Here we tested the hypothesis that treatment of cultured Caco-2 cells, a human intestinal epithelial cell line, with proteasome inhibitors induces the heat shock response and stimulates IL-6 production. Treatment of Caco-2 cells with one of the proteasome inhibitors MG-132 or lactacystin activated the transcription factor heat shock factors (HSF)-1 and -2 and upregulated cellular levels of the 72-kDa heat shock protein HSP-72. The same treatment resulted in increased gene and protein expression of IL-6, a response that was blocked by quercetin. Additional experiments revealed that the IL-6 gene promoter contains a HSF-responsive element and that the IL-6 gene may be regulated by the heat shock response. The present results suggest that proteasome inhibition induces heat shock response and IL-6 production in enterocytes and that IL-6 may be a heat shock-responsive gene, at least under certain circumstances. The observations are important considering the multiple biological roles of IL-6, both locally in the gut mucosa and systemically, and considering recent proposals in the literature to use proteasome inhibitors in the clinical setting to induce the heat shock response.

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mentioning

confidence: 48%

Proteasome inhibitors induce heat shock response and increase IL-6 expression in human intestinal epithelial cells

Pritts

Hungness²,

Hershko

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In previous studies, we have been particularly interested in mucosal production of IL-6 and have found evidence that mucosal IL-6 levels are increased during endotoxemia and sepsis in mice (23,48). Although multiple cell types may contribute to increased IL-6 production in the mucosa during inflammation, experiments in IL-1␤-treated cultured intestinal epithelial cells (22,30) suggest that the enterocyte is an important source of IL-6 during inflammation.…”

mentioning

confidence: 99%

Probiotics potentiate IL-6 production in IL-1β-treated Caco-2 cells through a heat shock-dependent mechanism

Reilly¹,

Poylin²,

Menconi³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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IL-6 may exert anti-inflammatory and protective effects in intestinal mucosa and enterocytes. The influence of probiotics on mucosal and enterocyte IL-6 production is not known. We tested the hypothesis that the probiotic bacteria Lactobacillus paracasei and Lactobacillus plantarum regulate IL-6 production in intestinal epithelial cells. Cultured Caco-2 cells were treated with 1 ng/ml of IL-1β in the absence or presence of different concentrations of L. paracasei or L. plantarum followed by measurement of IL-6 production. The role of heat shock response was examined by determining the expression of heat shock protein 70 (hsp70) and hsp27, by downregulating their expression with small interfering RNA (siRNA), or by treating cells with quercetin. Treatment of the Caco-2 cells with IL-1β resulted in increased IL-6 production, confirming previous reports from this laboratory. Probiotics alone did not influence IL-6 production, but the addition of probitoics to IL-1β-treated cells resulted in a substantial augmentation of IL-6 production. Treatment of the Caco-2 cells with live L. paracasei increased cellular levels of hsp70 and hsp27 and the potentiating effect on IL-6 production was inhibited by quercetin and by hsp70 or hsp27 siRNA. Results suggest that probiotics may enhance IL-6 production in enterocytes subjected to an inflammatory stimulus and that this effect may, at least in part, be heat shock dependent.

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“…IL-6 can probably be induced in most human tissues and cell types [24]. Numerous factors such as IL-1, TNF, endotoxin and reactive oxygen metabolites are capable of stimulating IL-6 expression [25][26][27][28]. Michalsky et al [5], using an in vitro model, showed that IL-6 and TNF were produced when enterocytes (Caco-2 cells) were exposed to E. coli bacteria.…”

Section: Discussionmentioning

confidence: 99%

Endotoxin and Cytokine Release in Strangulation Obstruction and in Partial Occlusion of the Mesenteric Artery in Pigs

Fevang¹,

Øvrebø²,

Svanes³

et al. 1999

Eur Surg Res

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Background: The study was performed to determine if endotoxin or the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) are liberated from strangulated or partially ischemic small bowel. Methods: Strangulation obstruction was induced by elevating pressure in a gasket placed around a loop of ileum until venous pressure reached 50 mm Hg. Low arterial flow in a loop of ileum was produced by arterial clamping reducing blood flow by 70%. A proximal bowel loop was used for control. Arterial blood flow was measured by transit time flowmetry. Blood samples were collected before and after 30, 90 and 180 min of strangulation or clamping. Plasma levels of endotoxin and cytokines (TNF, IL-1 and IL-6) were measured by limulus amebocyte lysate test and bioassays, respectively. Results: Strangulation obstruction caused more extensive mucosal damage than arterial clamping. Strangulation was followed by markedly increased venous concentration and release of IL-6 in the strangulated loop. Partial arterial occlusion did not cause increased release of IL-6. Strangulation or partial clamping did not influence the concentration of endotoxin, IL-1 or TNF in intestinal venous blood. Conclusions: Strangulation obstruction causes increased release of IL-6 to intestinal venous blood. IL-6 levels did not increase after 70% reduction of arterial blood flow. The early IL-6 increase was not detected in systemic blood. Strangulation did not cause early changes in plasma levels of endotoxin, TNF or IL-1.

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Endotoxin Stimulates Interleukin-6 Production in Intestinal Epithelial Cells

Abstract: Endotoxin and PGE2 stimulate IL-6 production in IEC-6 cells and interact synergistically. The endotoxin-stimulated IL-6 release may be regulated at the transcriptional level.

Cited by 54 publications

References 20 publications

Proteasome inhibitors induce heat shock response and increase IL-6 expression in human intestinal epithelial cells

Proteasome inhibitors induce heat shock response and increase IL-6 expression in human intestinal epithelial cells

Probiotics potentiate IL-6 production in IL-1β-treated Caco-2 cells through a heat shock-dependent mechanism

Endotoxin and Cytokine Release in Strangulation Obstruction and in Partial Occlusion of the Mesenteric Artery in Pigs

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