PPARα contributes to colonic protection in mice with DSS-induced colitis

Azuma, Yasutaka; Nishiyama, Kazuhiro; Matsuo, Yukiko; Kuwamura, Mitsuru; Morioka, Ai; Nakajima, Hidemitsu; Takeuchi, Tadayoshi

doi:10.1016/j.intimp.2010.07.007

Cited by 79 publications

(61 citation statements)

References 25 publications

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“…Disease activity index (DAI) was used for evaluating the grade and extent of intestinal inflammation (Azuma et al, 2010;Han et al, 2011). Body weight, stool consistency, and blood in the stool were monitored daily for DAI determination.…”

Section: Methodsmentioning

confidence: 99%

Ginsenosides Regulate PXR/NF-κB Signaling and Attenuate Dextran Sulfate Sodium–Induced Colitis

et al. 2015

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Pregnane X receptor (PXR) activation exhibits anti-inflammatory effects via repressing nuclear factor-kB (NF-kB); however, its overactivation may disrupt homeostasis of various enzymes and transporters. Here we found that ginsenosides restore PXR/NFkB signaling in inflamed conditions without disrupting PXR function in normal conditions. The effects and mechanisms of ginsenosides in regulating PXR/NF-kB signals were determined both in vitro and in vivo. Ginsenosides significantly inhibited NFkB activation and restored the expression of PXR target genes in tumor necrosis factor-a-stimulated LS174T cells. Despite not being PXR agonists, ginsenosides repressed NF-kB activation in a PXR-dependent manner. Ginsenosides significantly increased the physical association between PXR and the NF-kB p65 subunit and thereby decreased the nuclear translocation of p65. Ginsenoside Rb1 and compound K (CK) were major bioactive compounds in the regulating PXR/NF-kB signaling. Consistently, ginsenosides significantly attenuated dextran sulfate sodium-induced experimental colitis, which was associated with restored PXR/NF-kB signaling. This study indicates that ginsenosides may elicit antiinflammatory effects via targeting PXR/NF-kB interaction without disrupting PXR function in healthy conditions. Ginsenoside Rb1 and CK may serve as leading compounds in the discovery of new drugs that target PXR/NF-kB interaction in therapy for inflammatory bowel disease.

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Section: Methodsmentioning

confidence: 99%

Ginsenosides Regulate PXR/NF-κB Signaling and Attenuate Dextran Sulfate Sodium–Induced Colitis

et al. 2015

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“…In colitis models, fenofibrate treatment inhibited IFN-γ and IL-17 production, as well as decreased disease severity in IL-10 -/-mice (Lee et al, 2007). The synthetic ligand WY-14643 also showed reduced inflammatory cytokine production and disease severity in the DSSinduced colitis model (Azuma et al, 2010), suggesting that this ligand is a potential therapeutic for treating autoimmune diseases.…”

Section: Ppars In T Cells and Autoimmunitymentioning

confidence: 97%

The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases

Choi¹,

Bothwell

2012

Molecules and Cells

149

111

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Members of the nuclear receptor superfamily function as transcription factors involved in innate and adaptive immunity as well as lipid metabolism. These highly conserved proteins participate in ligand-dependent or -independent regulatory mechanisms that affect gene expression. Peroxisome proliferator-activated receptors (PPARs), which include PPARα, PPARβ/δ, and PPARγ, are a group of nuclear receptor proteins that play diverse roles in cellular differentiation, development, and metabolism. Each PPAR subfamily is activated by different endogenous and synthetic ligands. Recent studies using specific ligand treatments and cell type-specific PPAR knockout mice have revealed important roles for these proteins in T-cell-related autoimmune diseases. Moreover, PPARs have been shown to regulate T-cell survival, activation, and CD4 + T helper cell differentiation into the Th1, Th2, Th17, and Treg lineages. Here, we review the studies that provide insight into the important regulatory roles of PPARs in T-cell activation, survival, proliferation, differentiation, and autoimmune disease.

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“…Quantitative RT-PCR Quantitative real-time PCR was used to measure IL-19 and IFNγ mRNA expression in the ears and lymph nodes and was performed as described previously. 22) The primers for IL-19, IFNγ, and IL-17 were 5′-GCC ATG CAA ACT AAG GAC ACC-3′ and 5′-TTG GTC ATG CAG CAC ACA TC-3′, 5′-TAC ACA CTG CAT CTT GGC TTT G-3′ and 5′-CTT CCA CAT CTA TGC CAC TTG AG-3′, and 5′-GCT CCA GAA GGC CCT CAG A-3′ and 5′-AGC TTT CCC TCC GCA TTG A-3′, respectively. Hypoxanthine phosphoribosyltransferase (HPRT) mRNA was used to normalize mRNA expression.…”

Section: )mentioning

confidence: 99%