scholarly journals Olea europaea Suppresses Inflammation by Targeting TAK1-Mediated MAP Kinase Activation

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1540
Author(s):  
Chaoran Song ◽  
Mi-Yeon Kim ◽  
Jae Youl Cho
Keyword(s):  
Protein Kinase ◽  
Olea Europaea ◽  
Inflammatory Responses ◽  
Target Protein ◽  
Mitogen Activated Protein Kinase ◽  
Raw264.7 Cells ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
Protein Kinase Kinase ◽  
Olea Europaéa

Possessing a variety of medicinal functions, Olea europaea L. is widely cultivated across the world. However, the anti-inflammatory mechanism of Olea europaea is not yet fully elucidated. In this study, how the methanol extract of the leaves of Olea europaea (Oe-ME) can suppress in vitro inflammatory responses was examined in terms of the identification of the target protein. RAW264.7 and HEK293T cells were used to study macrophage-mediated inflammatory responses and to validate the target protein using PCR, immunoblotting, nuclear fraction, overexpression, and cellular thermal shift assay (CETSA) under fixed conditions. Oe-ME treatment inhibited the mRNA expression levels of cyclooxygenase (COX)-2, matrix metallopeptidase (MMP)-9, and intercellular adhesion molecule-1 (ICAM-1) in activated RAW264.7 cells. Oe-ME diminished the activation of activator protein (AP)-1 and the phosphorylation of its upstream signaling cascades, including extracellular signal regulated kinase (ERK), mitogen-activated protein kinase kinase 1/2 (MEK1/2), c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 3/6 (MKK3/6), p38, MKK7, and transforming growth factor-β-activated kinase 1 (TAK1), in stimulated-RAW264.7 cells. Overexpression and CETSA were carried out to verify that TAK1 is the target of Oe-ME. Our results suggest that the anti-inflammatory effect of Oe-ME could be attributed to its control of posttranslational modification and transcription of TAK1.

scholarly journals Nanostructured, Self-Assembling Peptide K5 Blocks TNF-αand PGE2Production by Suppression of the AP-1/p38 Pathway

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Woo Seok Yang ◽  
Yung Chul Park ◽  
Ji Hye Kim ◽  
Hye Ri Kim ◽  
Tao Yu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Inflammatory Responses ◽  
Nerve Repair ◽  
3D Cell Culture ◽  
Mitogen Activated Protein Kinase ◽  
Prostaglandin E ◽  
Transcriptional Level ◽  
Self Assembling ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Nanostructured, self-assembling peptides hold promise for a variety of regenerative medical applications such as 3D cell culture systems, accelerated wound healing, and nerve repair. The aim of this study was to determine whether the self-assembling peptide K5 can be applied as a carrier of anti-inflammatory drugs. First, we examined whether the K5 self-assembling peptide itself can modulate various cellular inflammatory responses. We found that peptide K5 significantly suppressed the release of tumor-necrosis-factor- (TNF-)αand prostaglandin E2(PGE2) from RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Similarly, there was inhibition of cyclooxygenase- (COX-) 2 mRNA expression assessed by real-time PCR, indicating that the inhibition is at the transcriptional level. In agreement with this finding, peptide K5 suppressed the translocation of the transcription factors activator protein (AP-1) and c-Jun and inhibited upstream inflammatory effectors including mitogen activated protein kinase (MAPK), p38, and mitogen-activated protein kinase kinase 3/6 (MKK 3/6). Whether this peptide exerts its effects via a transmembrane or cytoplasmic receptor is not clear. However, our data strongly suggest that the nanostructured, self-assembling peptide K5 may possess significant anti-inflammatory activity via suppression of the p38/AP-1 pathway.

Differential effect of p38 and MK2 kinase inhibitors on the inflammatory and toxicity biomarkers in vitro

2017 ◽  
Vol 37 (5) ◽  
pp. 521-531 ◽  
Author(s):  
RK Singh ◽  
M Diwan ◽  
SG Dastidar ◽  
AK Najmi
Keyword(s):  
Protein Kinase ◽  
Caspase 3 ◽  
Kinase Inhibitors ◽  
Inflammatory Responses ◽  
Interferon Γ ◽  
Mitogen Activated Protein Kinase ◽  
Toxicity Biomarkers ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Background: Many inflammatory responses including chemotaxis, production of nitric oxide, and modulation of pro-inflammatory cytokines in immunological cells are mediated by p38MAPK. Due to its pivotal role, p38MAPK has been extensively explored as a molecular target for inhibition of chronic inflammation; however, it has not been successful so far due to serious toxicity issues. Among several downstream substrates of p38, mitogen-activated protein kinase-activated protein kinase 2 (MK2) has been reported to be a direct and essential downstream component in regulation of innate immune and inflammatory responses. Thus, in this study, we aimed to understand relative molecular differences between p38 and MK2 kinase inhibition in terms of a comparative anti-inflammatory potential along with molecular regulation of toxicity biomarkers such as Phospho c-Jun N-Terminal Kinase (pJNK), caspase-3, and hepatic enzyme levels in relevant human cells in vitro. Results: Both p38 and MK2 inhibitors attenuated lipopolysaccharide-induced pro-inflammatory biomarkers expression. In addition, both these kinase inhibitors inhibited release of Th1 and Th17 cytokines in phytohemagglutinin-induced cells with MK2 inhibitor showing a better potency for inhibition of Th1 cytokine release, interferon-γ. In the mechanistic differentiation studies, p38 inhibitors displayed an increase in pJNK and caspase-3 activity in U937 cells and elevation in aspartate transaminase enzyme in HepG2 cells, whereas MK2 inhibitor did not show such adverse toxic effects. Conclusion: Taken together, inhibition of MK2 kinase can be a relatively preferred strategy as an anti-inflammatory therapy over direct inhibition of p38 kinase in p38MAPK pathway.

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