Anti‐inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL‐12 and up‐regulation of IL‐10 production

Säemann, Marcus D.; Böhmig, Georg A.; Österreicher, Christoph H.; Burtscher, Helmut; Parolini, Ornella; Diakos, Christos; Stöckl, Johannes; Hörl, Walter H.; Zlabinger, Gerhard J.

doi:10.1096/fj.00-0359fje

Cited by 395 publications

(287 citation statements)

References 56 publications

(65 reference statements)

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“…The ileum wall is interstratified with Peyer's patches, parts of the gut-associated lymphoid tissue. Cells from these patches have been shown to release anti-inflammatory cytokines such as IL10 after stimulation with probiotics, prebiotics or fermentation products thereof (Sä emann et al, 2000;Hosono et al, 2003;Roller et al, 2004). Therefore, it seems probable that fermentation products deriving from inulin degradation or secretory molecules from bacteria stimulated by inulin feeding are causative agents in this increase of IL10 expression.…”

Section: Discussionmentioning

confidence: 99%

Effects of the prebiotics inulin and lactulose on intestinal immunology and hematology of preruminant calves

Masanetz

Preißinger

Meyer

et al. 2011

Animal

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Prebiotics are suggested as an alternative to antibiotics in animal rearing. Fermentable substances such as inulin or lactulose have been proposed to stimulate the immune system and health by modulation of the intestinal flora and its fermentation products. In this study, effects of inulin and lactulose on the intestinal health and hematology of calves have been investigated. Both prebiotics significantly decreased thrombocyte counts in peripheral blood. Only inulin was able to increase hemoglobin concentration and hematocrit. Total leukocyte count was decreased by lactulose while both prebiotics tended to lower monocyte proportions. mRNA expression of inflammation-related markers in the intestine was also affected by both prebiotics hinting at a decreased inflammatory status. This may be due to a possible decrease in intestinal pathogen load that remains to be verified. Only mRNA amounts of interleukin 8 were increased by lactulose in mesenteric lymph nodes. In the ileum, expression of a proliferation marker was increased by inulin while an apoptosis-related gene was increased by both prebiotics. The results of this study show a clear effect of prebiotics on certain parameters associated with animal health and performance that remain to be studied in detail in future investigations.

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Section: Discussionmentioning

confidence: 99%

Effects of the prebiotics inulin and lactulose on intestinal immunology and hematology of preruminant calves

Masanetz

Preißinger

Meyer

et al. 2011

Animal

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“…For example, the combination of HDAC inhibitors trichostatin and butyrate have been shown to reduce IFN-␥ production by T cells (24). Leoni et al (10) have demonstrated significant reductions of TNF-␣, IL-1␤, and IFN-␥ in experimental endotoxemia and ConA-induced hepatic injury models with lower doses of SAHA than usually used as an antitumor agent.…”

Section: Discussionmentioning

confidence: 99%

Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect

Reddy

Maeda

Hotary

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

248

226

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Acute graft-versus-host disease (GVHD) and leukemic relapse are the two major obstacles to successful outcomes after allogeneic bone marrow transplantation (BMT), an effective therapy for hematological malignancies. Several studies have demonstrated that the dysregulation of proinflammatory cytokines and the loss of gastrointestinal tract integrity contribute to GVHD, whereas the donor cytotoxic responses are critical for graft-versus-leukemia (GVL) preservation. Suberoylanilide hydroxamic acid (SAHA) is currently in clinical trials as an antitumor agent; it inhibits the activity of histone deacetylases and at low doses exhibits antiinflammatory effects by reducing the production of proinflammatory cytokines. Using two well characterized mouse models of BMT, we have studied the effects of SAHA on GVHD severity and GVL activity. Administration of SAHA from day ؉3 to day ؉7 after BMT reduced serum levels of the proinflammatory cytokines and decreased intestinal histopathology, clinical severity, and mortality from acute GVHD compared with vehicle-treated animals. However, SAHA had no effect on donor T cell proliferative and cytotoxic responses to host antigens in vivo or in vitro. When mice received lethal doses of tumor cells at the time of BMT, administration of SAHA did not impair GVL activity and resulted in significantly improved leukemia-free survival by using two different tumor and donor͞recipient combinations. These findings reveal a critical role for histone deacetylase inhibition in the proinflammatory events contributing to GVHD and suggest that this class of pharmacologic agents may provide a strategy to reduce GVHD while preserving cytotoxic T cell responses to host antigens and maintaining beneficial GVL effects.

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“…Importantly, the recently reported ability of n-butyrate to inhibit antigen-specific immune reactivity in vivo indicates a potential clinical relevance (22,23). A central feature of n-butyrate-mediated inhibition of T-cell expansion is the abrogation of IL-2 production (17,24), which appears to be an important determinant of anergy induction. To obtain a better understanding of the mode of bacterial interference, we investigated the molecular mechanisms underlying the inhibition of IL-2 production by n-butyrate.…”

Section: T-cell Receptor (Tcr)mentioning

confidence: 99%

Novel Mode of Interference with Nuclear Factor of Activated T-cells Regulation in T-cells by the Bacterial Metaboliten-Butyrate

Diakos¹,

Prieschl²,

Säemann³

et al. 2002

Journal of Biological Chemistry

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The transcription factor nuclear factor of activated T-cells (NF-AT) plays an essential role in the activation of many early immune response genes. A dynamic equilibrium between calcineurin and cellular kinases controls its phosphorylation and thus regulates its activity by determining its subcellular localization. Here, we demonstrate that T-cell activation in the presence of the bacterial metabolite n-butyrate, which leads to inhibition of interleukin-2 transcription, is characterized by the maintenance of the activity of counter-regulatory kinases glycogen synthase kinase 3 and protein kinase A as well as persistence of intracellular cAMP levels, whereas calcium response and mitogen-activated protein kinase activation were indistinguishable from cells stimulated in the absence of n-butyrate. Nuclear binding of NF-AT was decreased but other transcription factors implicated in interleukin-2 expression such as AP1 and nuclear factor B were unaffected. The effect on NF-AT binding appeared to be the result of increased nuclear export because the export inhibitor leptomycin B completely restored nuclear binding of NF-AT. We, therefore, provide first evidence for interference with NF-AT regulation alternative to the currently understood inhibition of nuclear import. This mechanism might represent a bacterial strategy to subvert host defense, which could be of particular clinical importance in the gastrointestinal tract where high amounts of nbutyrate are physiologically present.

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Anti‐inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL‐12 and up‐regulation of IL‐10 production

Cited by 395 publications

References 56 publications

Effects of the prebiotics inulin and lactulose on intestinal immunology and hematology of preruminant calves

Effects of the prebiotics inulin and lactulose on intestinal immunology and hematology of preruminant calves

Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect

Novel Mode of Interference with Nuclear Factor of Activated T-cells Regulation in T-cells by the Bacterial Metaboliten-Butyrate

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