A Novel Peroxisome Proliferator-activated Receptor (PPAR)γ Agonist 2-Hydroxyethyl 5-chloro-4,5-didehydrojasmonate Exerts Anti-Inflammatory Effects in Colitis

Choo, Jieun; Lee, Yunna; Yan, Xinjia; Noh, Tae Hwan; Kim, Seong‐Jin; Son, Sujin; Pothoulakis, Charalabos; Moon, Hyung Ryong; Jung, Jee H.; Im, Eun‐Ok

doi:10.1074/jbc.m115.673046

Cited by 49 publications

(30 citation statements)

References 44 publications

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“…On the basis of its structural similarity to that of 15d-PGJ 2 , methyl jasmonate (J-11) was investigated for SIRT activity, and its functional mechanisms of regulation of cancer cell death pathways were investigated. A previous study indicated that an α-haloenone analog, J7, exhibited enhanced in vitro anti-inflammatory potency ( 14 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

Novel SIRT1 inhibitor 15-deoxy-Δ12,14-prostaglandin J2 and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells

et al. 2018

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Clinically relevant sirtuin (SIRT) inhibitors may possess antitumor activities. A previous study indicated that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) exhibited potent anticancer activity by SIRT1 inhibition. Therefore, the aim of the present study was to investigate whether its derivatives (J11-C1 and J19) exhibited anticancer activity against ovarian cancer SKOV3 cells. Cell viability was determined using an MTT assay. Cell cycle arrest, apoptosis and autophagy were determined using flow cytometry or western blot analysis. J11-Cl and J19 were less cytotoxic to SKOV3 cells compared with 15d-PGJ2. Molecular docking studies supported the interactions of 15d-PGJ2, J11-Cl and J19 with various amino acids in SIRT1 proteins. Similar to 15d-PGJ2, J11-C1 and J19 inhibited SIRT1 enzymatic activity and decreased SIRT1 expression levels in a concentration-dependent manner. J11-C1 induced apoptotic cell death more effectively compared with J19, which was associated with markedly decreased expression of the anti-apoptotic molecule B-cell lymphoma 2 (Bcl-2). Furthermore, the levels of light chain 3-II (LC3-II) and beclin-1 were clearly induced in SKOV3 cells treated with J11-Cl. Thus, 15d-PGJ2 and its derivatives exhibited anticancer activity possibly by inducing apoptotic or autophagic cell death pathways. Collectively, the results of the present study suggest that 15d-PGJ2 and its derivatives exerted antitumor activity by selectively modulating the expression of genes associated with cell cycle arrest, apoptosis and autophagy. Notably, J11-C1 is a novel candidate SIRT1 inhibitor with anticancer activity.

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Section: Introductionmentioning

confidence: 99%

Novel SIRT1 inhibitor 15-deoxy-Δ12,14-prostaglandin J2 and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells

et al. 2018

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“…The impaired regulatory function after knockout of PPAR‐ γ in B cells was not due to reduced naive splenic CD5 + CD1d hi Breg cell generation, but instead to the activation‐induced IL‐10 + CD5 + CD1d hi Breg cell expansion. Our group and other groups recently described that nuclear factor‐ κ B and nuclear factor of activated T‐cell signal inhibition, which had been observed after PPAR‐ γ activation in effector cells, could dampen Breg cell activation . We cannot exclude the possibility that paradoxical effects of PPAR‐ γ activation on Breg cells initiated by a different immune balance might sometimes occur during immune responses.…”

Section: Discussionmentioning

confidence: 86%

“…Both natural and synthesized ligands such as rosiglitazone can bind to PPAR‐ γ . PPAR‐ γ activation was first noted to treat diabetes; its additional anti‐inflammatory and immunosuppressive functions were recently demonstrated through its ability to ameliorate CHS, EAE, arthritis etc . Whole‐body PPAR‐ γ +/− mice were more susceptible to autoimmune and inflammatory diseases such as immune arthritis and EAE, which further indicated that endogenous PPAR‐ γ activation also limited inflammation and immune responses.…”

Section: Introductionmentioning

confidence: 99%

B‐cell‐specific‐peroxisome proliferator‐activated receptor γ deficiency augments contact hypersensitivity with impaired regulatory B cells

Wang

Zhou

et al. 2018

Immunology

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Nuclear receptor peroxisome proliferator-activated receptor c (PPAR-c) activation can prevent immunoinflammatory disorders and diabetes. B cells play protective roles during inflammation as well. However, the roles of endogenous PPAR-c in the regulatory properties of B cells to relieve inflammation remain unknown. Here, we developed B-cell-specific PPARc knockout (B-PPAR-c À/À ) mice and found that the conditional deletion of PPAR-c in B cells resulted in exaggerated contact hypersensitivity (CHS). Meanwhile, interferon-c (IFN-c) of CD4 + CD8 + T cells was up-regulated in B-PPAR-c À/À mice in CHS. This showed that the regulatory function of B cells in B-PPAR-c À/À mice declined in vivo. Whereas splenic CD5 + CD1d hi regulatory B-cell numbers and peripheral regulatory T-cell numbers were not changed in naive B-PPAR-c À/À mice. Loss of PPAR-c in B cells also did not affect either CD86 or FasL expression in splenic CD5 + CD1d hi regulatory B cells after activation. Notably, interleukin-10 (IL-10) production in CD5 + CD1d hi regulatory B cells reduced in B-PPAR-c-deficient mice. In addition, functional IL-10-producing CD5 + CD1d hi regulatory B cells decreased in B-PPAR-c À/À mice in the CHS model. These findings were in accordance with augmented CHS. The current work indicated the involvement of endogenous PPAR-c in the regulatory function of B cells by disturbing the expansion of IL-10-positive regulatory B cells.

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“…PPAR-γ reduces the expression levels of pro-inflammatory chemokines, including chemokine (C-C motif) ligand 20, CXC ligand (CXCL)2, CXCL3 and chemokine (C-X3-C motif) ligand 1 (CX3CL1) in colon tissues. It has been shown that increasing the transcriptional activity of PPAR-γ can modulate inflammatory signaling pathways, suggesting a novel target for therapeutic agents ( 117 ). The investigation of inflammatory markers in vascular disorders reveals augmented levels of circulating cytokines and chemokines among carriers of classic risk factors for atherosclerosis.…”

Section: Potential Role Of Ppar Agonists In the Treatment Of Cabmentioning

confidence: 99%

The molecular mechanisms of action of PPAR-γ agonists in the treatment of corneal alkali burns?(Review)

Zhou

Zhang

et al. 2016

Int J Mol Med

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Corneal alkali burns (CAB) are characterized by injury-induced inflammation, fibrosis and neovascularization (NV), and may lead to blindness. This review evaluates the current knowledge of the molecular mechanisms responsible for CAB. The processes of cytokine production, chemotaxis, inflammatory responses, immune response, cell signal transduction, matrix metalloproteinase production and vascular factors in CAB are discussed. Previous evidence indicates that peroxisome proliferator-activated receptor γ (PPAR-γ) agonists suppress immune responses, inflammation, corneal fibrosis and NV. This review also discusses the role of PPAR-γ as an anti-inflammatory, anti-fibrotic and anti-angiogenic agent in the treatment of CAB, as well as the potential role of PPAR-γ in the pathological process of CAB. There have been numerous studies evaluating the clinical profiles of CAB, and the aim of this systematic review was to summarize the evidence regarding the treatment of CAB with PPAR-γ agonists.

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A Novel Peroxisome Proliferator-activated Receptor (PPAR)γ Agonist 2-Hydroxyethyl 5-chloro-4,5-didehydrojasmonate Exerts Anti-Inflammatory Effects in Colitis

Cited by 49 publications

References 44 publications

Novel SIRT1 inhibitor 15-deoxy-Δ12,14-prostaglandin J2 and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells

Novel SIRT1 inhibitor 15-deoxy-Δ12,14-prostaglandin J2 and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells

B‐cell‐specific‐peroxisome proliferator‐activated receptor γ deficiency augments contact hypersensitivity with impaired regulatory B cells

The molecular mechanisms of action of PPAR-γ agonists in the treatment of corneal alkali burns?(Review)

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