MAPK–PPARα/γ signal transduction pathways are involved in Chlamydia pneumoniae-induced macrophage-derived foam cell formation

Cheng, Bei; Wu, Xiujie; Sun, Shan; Qing, WU; Mei, Chunli; Xu, Qiumei; Wu, Jianping; He, Ping

doi:10.1016/j.micpath.2014.03.001

Cited by 23 publications

(27 citation statements)

References 30 publications

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“…First, it has been reported that JNK1 inhibits the phosphorylation of serine residues on insulin receptor substrate 1, thus inducing insulin resistance and obesity‐induced inflammation . In addition, in lipid metabolism, the complicated mechanism by which JNK1 promotes steatosis which involves hepatic and/or peripheral effects, might be related to PPARα/γ . Furthermore, there is also evidence that JNK activation might contribute to diet‐induced inflammation .…”

Section: Discussionmentioning

confidence: 99%

The novel intracellular protein CREG inhibits hepatic steatosis, obesity, and insulin resistance

Zhang

Zhao

Tian³

et al. 2017

Hepatology

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The results of our study provides evidence that CREG is a robust suppressor of hepatic steatosis and metabolic disorders through its direct interaction with ASK1 and the resultant inactivation of ASK1-JNK1 signaling. This study offers insights into NAFLD pathogenesis and its complicated pathologies, such as obesity and insulin resistance, and paves the way for disease treatment through targeting CREG. (Hepatology 2017;66:834-854).

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Section: Discussionmentioning

confidence: 99%

The novel intracellular protein CREG inhibits hepatic steatosis, obesity, and insulin resistance

Zhang

Zhao

Tian³

et al. 2017

Hepatology

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“…Data concerning the role of MAPK for lipoprotein uptake by human monocytes/macrophages are sparse and contradictory. Although 2 studies suggested that LDL uptake by THP‐1 cells (31) or cholesterol ester accumulation in THP‐1 cells (32), respectively, is promoted by p38 MAPK, a third report suggested that p38 inhibition had no obvious effect on lipid accumulation in LDL‐treated THP‐1 macrophages (33). The interpretation of these findings, however, is difficult because nonselective p38 MAPK inhibitors were used exclusively.…”

Section: Discussionmentioning

confidence: 99%

Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL‐stimulated human monocytes: implications for atherosclerosis

et al. 2016

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The first ATP-competitive p38α MAPK/MAPK14 inhibitor with excellent in vivo efficacy and selectivity, skepinone-L, is now available. We investigated the impact of selective p38α MAPK/MAPK14 inhibition on enzymatically modified LDL (eLDL) stimulated human monocytes with its implications for atherosclerosis. Among the different p38 MAPK isoforms, p38α/MAPK14 was the predominantly expressed and activated isoform in isolated human peripheral blood monocytes. Moreover, eLDL colocalized with macrophages positive for p38α MAPK/MAPK14 in human carotid endarterectomy specimens. Using the human leukemia cell line THP-1 and/or primary monocyte-derived macrophages, skepinone-L inhibited eLDL-induced activation of the p38 MAPK pathway, inhibited eLDL induced expression of both cluster of differentiation 36 (CD36) and ATP-binding cassette, subfamily A, member 1 (ABCA1), without a net effect on foam cell formation, had a cell- and time-dependent effect on eLDL-triggered apoptosis, and inhibited eLDL-stimulated secretion of IL-8 and MIP-1β/CCL4 (macrophage inflammatory protein-1β/chemokine, CC motif, ligand 4). Inhibition of a key signaling molecule of the p38 MAPK pathway, p38α MAPK/MAPK14, by selective inhibitors like skepinone-L, conclusively facilitates elucidation of the impact of the complex network of p38 MAPK signaling on atherogenesis and might provide a promising therapeutic tool to prevent inflammatory cascades in atherosclerosis.-Cheng, F., Twardowski, L., Fehr, S., Aner, C., Schaeffeler, E., Joos, T., Knorpp, T., Dorweiler, B., Laufer, S., Schwab, M., Torzewski, M. Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human monocytes: implications for atherosclerosis.

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“…Peroxisome proliferator-activated receptors (PPARs) α and γ are members of the nuclear hormone receptor superfamily that regulates the metabolism of glucose and lipids [9]. PPARα and γ can prevent inflammation in white adipose tissue and enhance the expression of adiponectin [10]. PPARα is a downstream effector of p38 kinase-dependent stress-activated signaling in the heart, and the activation of PPARα can ameliorate the development of insulin resistance [11].…”

Section: Introductionmentioning

confidence: 99%

Mineralocorticoid Receptor Blockade Improves Insulin Sensitivity in the Rat Heart and a Possible Molecular Mechanism

Wang

Zhou

et al. 2016

Cell Physiol Biochem

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Background/Aims: Extensive research has explored the role of aldosterone in insulin resistance. Recent evidence suggests that the mineralocorticoid receptor (MR) mediates aldosterone-induced dysregulation of cytokines, and most of this research has focused on adjustments in fat tissue and adipocytes. However, the direct effect of MR blockade on insulin resistance in cardiomyocytes remains largely unknown. In the present study, we investigated whether MR blockade improves insulin-sensitizing factors in insulin-resistant rats and attenuates the dysregulation of the aldosterone-related transport of adiponectin and glucose in cardiomyocytes and examined the underlying mechanisms. Methods: The effects of aldosterone, MR inhibitors (e.g., eplerenone), a peroxisome proliferator-activated receptor (PPAR) α agonist, and a p38 mitogen-activated protein kinase (MAPK) inhibitor on adiponectin and glucose transport were studied at the mRNA and protein levels in vitro and in vivo. Results: Our data revealed that aldosterone reduced the expression of adiponectin and inhibited the transport of glucose in cardiomyocytes and that MR blockade reversed these affects. In vivo, MR blockade improved insulin-sensitive parameters and increased adiponectin expression in the myocardia of high-fat diet rats. Furthermore, aldosterone promoted p38MAPK expression but negatively affected PPARα expression, and the downregulation of adiponectin by aldosterone was reversed by MR blockade, a PPARα agonist, and a p38 MAPK inhibitor. Conclusion: The above results suggested that aldosterone promoted insulin resistance in the heart and that this effect could be partly reversed by MR blockade through signal transduction in the P38 MAPK pathway and PPARα.

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MAPK–PPARα/γ signal transduction pathways are involved in Chlamydia pneumoniae-induced macrophage-derived foam cell formation

Cited by 23 publications

References 30 publications

The novel intracellular protein CREG inhibits hepatic steatosis, obesity, and insulin resistance

The novel intracellular protein CREG inhibits hepatic steatosis, obesity, and insulin resistance

Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL‐stimulated human monocytes: implications for atherosclerosis

Mineralocorticoid Receptor Blockade Improves Insulin Sensitivity in the Rat Heart and a Possible Molecular Mechanism

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