The p38 MAPK inhibitor SB203580 differentially modulates LPS-induced interleukin 6 expression in macrophages

Shi, Qinghai; Cheng, Liping; Liu, Zhengxiang; Hu, Keyan; Ran, Juntao; Ge, Di; Fu, Jianfeng

doi:10.5114/ceji.2015.54586

Cited by 23 publications

(18 citation statements)

References 21 publications

(1 reference statement)

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“…We also found p38 attenuation in CWG-treated cells. P38 kinase is involved in LPS-stimulated TNF-α and IL-6 production by directly modulating these cytokine mRNA half-life or modulating cytosolic phospholipase A2 -mediated NF-κB activation [ 30 , 31 ]. These events may account for the observed difference in the anti-inflammatory properties of CWG and UWG.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity of Citric Acid-Treated Wheat Germ Extract in Lipopolysaccharide-Stimulated Macrophages

Jeong

Choi²,

Lee³

et al. 2017

Nutrients

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Until recently, fermentation was the only processing used to improve the functionality of wheat germ. The release of 2,6-dimethoxy-1,4-benzoquinone (DMBQ) from hydroquinone glycosides during the fermentation process is considered a marker of quality control. Here, we treated wheat germ extract with citric acid (CWG) to release DMBQ and examined the anti-inflammatory activity of this extract using a lipopolysaccharide-activated macrophage model. Treatment of wheat germ with citric acid resulted in detectable release of DMBQ but reduced total phenolic and total flavonoid contents compared with untreated wheat germ extract (UWG). CWG inhibited secretion of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-12 and the synthesis of cyclooxygenase-2, while UWG only decreased IL-12 production. CWG and UWG induced high levels of anti-inflammatory IL-10 and heme oxygenase-1. CWG specifically inhibited phosphorylation of NF-κB p65 and p38 kinase at 15 min after LPS stimulation. Our study showed that citric acid treatment enhanced the anti-inflammatory activity of wheat germ extract.

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity of Citric Acid-Treated Wheat Germ Extract in Lipopolysaccharide-Stimulated Macrophages

Jeong

Choi²,

Lee³

et al. 2017

Nutrients

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“…Furthermore, the JNK inhibitor SP600125 (Bennett et al, 2001 ; Nieminen et al, 2006 ) but not the p38 inhibitor SB203580 (Cuenda et al, 1995 ; Shi et al, 2015 ) reduced LPS-induced mPGES-1 expression in a manner comparable to that of dexamethasone (Figures 6A,B ).…”

Section: Resultsmentioning

confidence: 94%

Microsomal Prostaglandin E Synthase-1 Expression in Inflammatory Conditions Is Downregulated by Dexamethasone: Seminal Role of the Regulatory Phosphatase MKP-1

2017

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Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme situated downstream of cyclo-oxygenase-2, promoting the excessive PGE2 production in inflammation. Dexamethasone is known to suppress mPGES-1 but the mechanisms regulating mPGES-1 expression remain poorly known. MKP-1 is a phosphatase controlling the proinflammatory MAP kinase pathways p38 and JNK, thus limiting the inflammatory responses. We have now investigated the role of MKP-1 and MAP kinases p38 and JNK in the regulation of mPGES-1 expression by dexamethasone. Dexamethasone increased MKP-1 and decreased mPGES-1 expression in J774 macrophages and in peritoneal macrophages from wild-type but not from MKP-1 deficient mice. Dexamethasone also reduced p38 and JNK phosphorylation along with enhancement of MKP-1, while inhibition of JNK reduced mPGES-1 expression. These findings were also translated to in vivo conditions as dexamethasone downregulated mPGES-1 expression in paw inflammation in wild-type but not in MKP-1 deficient mice. In conclusion, dexamethasone was found to downregulate mPGES-1 expression through enhanced MKP-1 expression and reduced JNK phosphorylation in inflammatory conditions. The results extend the understanding on the regulation of mPGES-1 expression and highlight the potential of MKP-1 as an anti-inflammatory drug target.

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“…Chronic inflammation associated with tumour development is promoted by several mechanisms involved in the production of proangiogenic factors, matrix metalloproteinases (MMPs), and damage-associated molecular pattern molecules (DAMPs). All of the above leads to MDSC accumulation and MDSC suppressive effects [ 12 , 35 - 39 ].…”

Section: Mdscs In Tumour Microenvironmentmentioning

confidence: 99%

Myeloid-derived suppressor cells in ovarian cancer: friend or foe?

Walankiewicz

Grywalska

Polak

et al. 2017

cejoi

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Although previous decades contributed to major progress in targeted therapy of many malignancies, the treatment of gynaecological cancers remains a challenging task. In the evidence of rising cancer mortality, the search for new methods of treatment is a dire need. Exploring the mechanisms of interaction between tumour cells and host immune response may allow the introduction of new, effective therapies – not as toxic and far more efficient than conventional methods of cancer treatment. Epithelial ovarian cancer (EOC) is typically diagnosed at advanced stages. Its incidence and mortality rate is high. Powerful diagnostic tools for this kind of cancer are still under investigation. Multiple mechanisms existing in the ovarian tumour network create a specific immunosuppressive microenvironment, in which accumulation of myeloid-derived suppressor cells (MDSCs) may be a critical component for diagnosis and treatment. This review attempts to verify current knowledge on the role of MDSCs in EOC.

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The p38 MAPK inhibitor SB203580 differentially modulates LPS-induced interleukin 6 expression in macrophages

Abstract: The p38 mitogen-activated protein kinase (MapK)

Cited by 23 publications

References 21 publications

Anti-Inflammatory Activity of Citric Acid-Treated Wheat Germ Extract in Lipopolysaccharide-Stimulated Macrophages

Anti-Inflammatory Activity of Citric Acid-Treated Wheat Germ Extract in Lipopolysaccharide-Stimulated Macrophages

Microsomal Prostaglandin E Synthase-1 Expression in Inflammatory Conditions Is Downregulated by Dexamethasone: Seminal Role of the Regulatory Phosphatase MKP-1

Myeloid-derived suppressor cells in ovarian cancer: friend or foe?

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