Endotoxemia and IL-1β Stimulate Mucosal IL-6 Production in Different Parts of the Gastrointestinal Tract

Wang, Quan; Wang, Jing Jing; Boyce, Steven T.; Fischer, Josef E.; Hasselgren, Per-Olof

doi:10.1006/jsre.1998.5288

Cited by 39 publications

(33 citation statements)

References 16 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).…”

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confidence: 51%

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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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confidence: 51%

“…ple, mucosal production of certain acute phase proteins (28,29,47,50) and cytokines (13,25,27,49) is increased in these conditions, and some of these substances may influence mucosal integrity and regulate intestinal permeability (15,51).…”

mentioning

confidence: 99%

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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“…The results of the present study showed that the presence of LPS resulted in increased expression of IL-1β, IL-6, IL-8, TNF-α in the plasma and colon tissue. Wang et al (27) previously demonstrated that both TNF-α and IL-1β may be involved in the regulation of gastrointestinal IL-6 production during endotoxemia in mice.…”

Section: Discussionmentioning

confidence: 99%

Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway

Zhang

Jiao

et al. 2015

Molecular Medicine Reports

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Abstract. Sepsis is one of the leading causes of mortality in severe systemic inflammatory syndrome. The endotoxin-induced inflammatory response has been linked to the development of sepsis. Rhein is a lipophilic anthraquinone isolated from Rheum rhabarbarum (rhubarb), which has a protective effect on intestinal damage in vivo. However, the underlying mechanism responsible for the protective effects of rhein remains to be elucidated. In the present study, mice were exposed to 20 mg/kg lipopolysaccharide (LPS), prior to being treated with either 100 mg/kg rhein or 0.3 mg/kg toll-like receptor 4 (TLR4) signaling inhibitor TAK-242. In the rhein-treated mice, the colon length (cm) was extended and colon injury was attenuated. In addition, treatment with rhein significantly decreased the expression levels of the LPS-induced inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α, in both the plasma and colon tissue. However, mice treated with TAK-242 exhibited increased expression levels of IL-10, as determined by ELISA and western blot analysis. In addition, immunohistochemistry and western blot analyses demonstrated that treatment with rhein was able to reduce TLR4 expression and inhibit nuclear factor-κB (NF-κB) phosphorylation in colon tissue. Furthermore, LPS induction was blocked by TAK-242. These results demonstrate that the observed rhein-attenuated inflammatory response during sepsis may be achieved via the TLR4 NF-κB signaling pathway. In conclusion, the results of the present study provide a novel insight into the protective effects of rhein on LPS-induced intestinal inflammation, and demonstrate that rhein may act as a beneficial therapeutic agent in the treatment of sepsis-induced intestinal damage.

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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.…”

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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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Endotoxemia and IL-1β Stimulate Mucosal IL-6 Production in Different Parts of the Gastrointestinal Tract

Cited by 39 publications

References 16 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

Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway

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

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