MAPK signalling pathways as molecular targets for anti-inflammatory therapy—from molecular mechanisms to therapeutic benefits

Kamińska, Bożena

doi:10.1016/j.bbapap.2005.08.017

Cited by 1,124 publications

(812 citation statements)

References 103 publications

Supporting

Mentioning

787

Contrasting

Unclassified

Order By: Relevance

“…Mitogenactivated protein kinases (MAPKs) are implicated in inflammatory signaling, which facilitates the production of inflammatory mediators (Kaminska, 2005). ERK may modulate mTOR signaling and contribute to disease progression through the phosphorylation and inactivation of TSC2 (Ma et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

LL-37 attenuates inflammatory impairment via mTOR signaling-dependent mitochondrial protection

Sun

Zheng

et al. 2014

The International Journal of Biochemistry & Cell Biology

View full text Add to dashboard Cite

a b s t r a c tThe human cationic antimicrobial protein LL-37 is a multifunctional host defense peptide with a wide range of immunomodulatory activities. Previous work has shown that LL-37 exerts both pro-and antiinflammatory effects. The role of mitochondria in the skin inflammatory effects of LL-37 has not been well studied. Therefore, our aim was to investigate the immunomodulatory effect of LL-37 in HaCaT cells and to delineate the underlying mechanisms related to mitochondrial function. Immunohistochemistry results from tissue microarrays showed strong cytoplasmic LL-37 staining in inflammatory cells in chronic dermatic inflammation. Using exogenous LL-37 stimulation and LL-37 knockdown and overexpression, LL-37 was demonstrated to dramatically reduce the mRNA levels and protein secretion of inflammatory cytokines including IL-6, IL-8, IL-1␣ and tumor necrosis factor-␣ (TNF-␣), which are induced by lipopolysaccharides (LPS). The anti-inflammatory effects of LL-37 are dependent upon its ability to increase mitochondrial biogenesis and to maintain mitochondrial homeostasis. Furthermore, we observed that LL-37 enhances the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and mammalian target of rapamycin (mTOR). The mTOR inhibitor rapamycin can neutralize the protective effects of LL-37 on mitochondria. In conclusion, these results suggest that high LL-37 expression levels correlate with chronic skin inflammation; mitochondrial dysfunction occurs in HaCaT cells during inflammation; and LL-37 attenuates inflammatory impairment by stimulating mitochondrial biogenesis and protecting mitochondrial function, which are dependent upon mTOR signaling. These findings provide new insights into targeting mitochondria with LL-37 to prevent skin inflammatory reactions.

show abstract

Section: Discussionmentioning

confidence: 99%

LL-37 attenuates inflammatory impairment via mTOR signaling-dependent mitochondrial protection

Sun

Zheng

et al. 2014

The International Journal of Biochemistry & Cell Biology

View full text Add to dashboard Cite

show abstract

“…It has been reported that inhibitors of p38 and JNK have anti-inflammatory effects due to inhibition of the expression of inflammatory mediators. Many novel drugs that modulate the activity of the JNK and p38 MAPK pathways have shown promise for treating chronic inflammatory diseases [37,38] . However, compared with JNK and p38 MAPK, there is relatively little information regarding the role of the ERK cascade in inflammatory processes [39] .…”

Section: Discussionmentioning

confidence: 99%

Compound FLZ inhibits lipopolysaccharide-induced inflammatory effects via down-regulation of the TAK-IKK and TAK-JNK/p38MAPK pathways in RAW264.7 macrophages

Pang

Liu

2009

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim:The aim of this study was to investigate the effect of the squamosamide derivative FLZ (N-2-(4-hydroxy-phenyl)-ethyl-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide) on lipopolysaccharide (LPS)-induced inflammatory mediator production and the underlying mechanism in RAW264.7 macrophages. Methods: RAW264.7 cells were preincubated with non-toxic concentrations of compound FLZ (1, 5, and 10 µmol/L) for 30 min and then stimulated with 10 μg/L LPS. The production of nitric oxide (NO), the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), and the activation of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways were examined. Results: FLZ significantly inhibited the LPS-induced production of NO, as well as the expression of iNOS and COX-2 at both the RNA and the protein levels in RAW264.7 cells. The LPS-induced increase in the DNA binding activity of NF-κB and activator protein 1 (AP-1), the nuclear translocation of NF-κB p65, the degradation of the inhibitory κBα protein (IκBα) and the phosphorylation of IκBα, IκB kinase (IKK) α/β, c-Jun NH 2 -terminal kinase (JNK) and p38 MAPKs were all suppressed by FLZ. However, the phosphorylation of extracellular signal-regulated kinase (ERK) was not affected. Further study revealed that FLZ inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), which is an upstream signaling molecule required for IKKα/β, JNK and p38 activation. Conclusion: FLZ inhibited the LPS-induced production of inflammatory mediators at least partly through the downregulation of the TAK-IKK and TAK-JNK/p38MAPK pathways.

show abstract

“…For instance, Akt can phosphorylate IκB, leading to NF-κB release and activation (Huang and Chen, 2009). The MAPK pathways, which are extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 MAPK pathways in particular (Herlaar and Brown, 1999), also regulate the synthesis of inflammation mediators at the level of transcription and translation through activation of NF-κB and AP-1 transcription factors (Kaminska, 2005).…”

Section: Introductionmentioning

confidence: 99%

Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages

Zhang

Meng

et al. 2014

Journal of Ethnopharmacology

166

View full text Add to dashboard Cite

MAPK signalling pathways as molecular targets for anti-inflammatory therapy—from molecular mechanisms to therapeutic benefits

Cited by 1,124 publications

References 103 publications

LL-37 attenuates inflammatory impairment via mTOR signaling-dependent mitochondrial protection

LL-37 attenuates inflammatory impairment via mTOR signaling-dependent mitochondrial protection

Compound FLZ inhibits lipopolysaccharide-induced inflammatory effects via down-regulation of the TAK-IKK and TAK-JNK/p38MAPK pathways in RAW264.7 macrophages

Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages

Contact Info

Product

Resources

About