Gene Expression Profile of Coronary Artery Cells Treated With Nonsteroidal Anti-inflammatory Drugs Reveals Off-target Effects

PPARαs are nuclear receptors highly expressed in colon cells. They can be activated by the fibrates (clofibrate, ciprofibrate etc.) used to treat hyperlipidemia. Since PPARαtranscriptional activity can be negatively regulated by JNK, the inhibition of JNK activity could increase the effectiveness of PPARαligands. We analysed the effects of AS601245 (a JNK inhibitor) and clofibrate alone or in association, on proliferation, apoptosis, differentiation and the gene expression profile of CaCo-2 human colon cancer cells. Proliferation was inhibited in a dose-dependent way by clofibrate and AS601245. Combined treatment synergistically reduced cell proliferation, cyclin D1 and PCNA expression and induced apoptosis and differentiation. Reduction of cell proliferation, accompanied by the modulation of p21 expression was observed in HepG2 cells, also. Gene expression analysis revealed that some genes were highly modulated by the combined treatment and 28 genes containing PPRE were up-regulated, while clofibrate alone was ineffective. Moreover, STAT3 signalling was strongly reduced by combined treatment. After combined treatment, the binding of PPARαto PPRE increased and paralleled with the expression of the PPAR coactivator MED1. Results demonstrate that combined treatment increases the effectiveness of both compounds and suggest a positive interaction between PPARαligands and anti-inflammatory agents in humans.

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The Shared Crosstalk of Multiple Pathways Involved in the Inflammation between Rheumatoid Arthritis and Coronary Artery Disease Based on a Digital Gene Expression Profile

PLoS ONE ◽

10.1371/journal.pone.0113659 ◽

2014 ◽

Vol 9 (12) ◽

pp. e113659 ◽

Cited By ~ 8

Author(s):

Xuyan Niu ◽

Cheng Lu ◽

Cheng Xiao ◽

Zhiguo Zhang ◽

Miao Jiang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Gene Expression Profile ◽

Expression Profile ◽

Digital Gene Expression ◽

Digital Gene Expression Profile ◽

Artery Disease

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Peripheral blood gene expression profile of atherosclerotic coronary artery disease in patients of different ethnicity in Malaysia

Journal of Cardiology ◽

10.1016/j.jjcc.2012.05.009 ◽

2012 ◽

Vol 60 (3) ◽

pp. 192-203 ◽

Cited By ~ 13

Author(s):

Mohd Hafiz Ngoo Abdullah ◽

Zulhabri Othman ◽

Hamdan Mohd Noor ◽

Siti Suri Arshad ◽

Ahmad Khairuddin Mohd Yusof ◽

...

Keyword(s):

Gene Expression ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Gene Expression Profile ◽

Expression Profile ◽

Peripheral Blood ◽

Blood Gene Expression ◽

Peripheral Blood Gene Expression ◽

Artery Disease

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Alliin, a Garlic (Allium sativum) Compound, Prevents LPS-Induced Inflammation in 3T3-L1 Adipocytes

Mediators of Inflammation ◽

10.1155/2013/381815 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 31

Author(s):

Saray Quintero-Fabián ◽

Daniel Ortuño-Sahagún ◽

Manuel Vázquez-Carrera ◽

Rocío Ivette López-Roa

Keyword(s):

Gene Expression ◽

Gene Expression Profile ◽

Expression Profile ◽

Allium Sativum ◽

Serum Levels ◽

Organosulfur Compounds ◽

Inflammatory Gene Expression ◽

Cytokine Levels ◽

Anti Inflammatory ◽

Neuroprotective Actions

Garlic (Allium sativumL.) has been used to alleviate a variety of health problems due to its high content of organosulfur compounds and antioxidant activity. The main active component is alliin (S-allyl cysteine sulfoxide), a potent antioxidant with cardioprotective and neuroprotective actions. In addition, it helps to decrease serum levels of glucose, insulin, triglycerides, and uric acid, as well as insulin resistance, and reduces cytokine levels. However its potential anti-inflammatory effect is unknown. We examined the effects of alliin in lipopolysaccharide- (LPS-) stimulated 3T3-L1 adipocytes by RT-PCR, Western blot, and microarrays analysis of 22,000 genes. Incubation of cells for 24 h with 100 μmol/L alliin prevented the increase in the expression of proinflammatory genes, IL-6, MCP-1, and Egr-1 in 3T3-L1 adipocytes exposed to 100 ng/mL LPS for 1 h. Interestingly, the phosphorylation of ERK1/2, which is involved in LPS-induced inflammation in adipocytes, was decreased following alliin treatment. Furthermore, the gene expression profile by microarrays evidentiate an upregulation of genes involved in immune response and downregulation of genes related with cancer. The present results have shown that alliin is able to suppress the LPS inflammatory signals by generating an anti-inflammatory gene expression profile and by modifying adipocyte metabolic profile.

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