scholarly journals Neutrophil Chemotaxis and NETosis in Murine Chronic Liver Injury via Cannabinoid Receptor 1/Gαi/o/ROS/p38 MAPK Signaling Pathway

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 373 ◽  
Author(s):  
Xuan Zhou ◽  
Le Yang ◽  
Xiaoting Fan ◽  
Xinhao Zhao ◽  
Na Chang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Cannabinoid Receptors ◽  
Neutrophil Function ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Marker Genes ◽  
Neutrophil Chemotaxis ◽  
Liver Inflammation

Neutrophils play an essential role in the control of inflammatory diseases. However, whether cannabinoid receptors (CBs) play a role in neutrophil chemotaxis and NETosis in sterile liver inflammation remains unknown. The expression of marker genes on neutrophils was characterized by FACS, immunofluorescence, qRT-PCR, and Western blot. The amount of neutrophils was significantly elevated from 7 days and reached the peak at 2 weeks in carbon tetrachloride (CCl4)-treated mouse liver. The mRNA expression of neutrophil marker Ly6G had positive correlation with CB1 and CB2 expression in injured liver. In vitro CBs were abundantly expressed in isolated neutrophils and CB1 agonist ACEA promoted the chemotaxis and cytoskeletal remodeling, which can be suppressed by CB1 antagonist AM281. Moreover, ACEA induced NETosis, myeloperoxidase release from lysosome and ROS burst, indicating neutrophil activation, via Gαi/o. Conversely, CB2 agonist JWH133 had no effect on neutrophil function. ROS and p38 MAPK signaling pathways were involved in CB1-mediated neutrophil function, and ROS was upstream of p38 MAPK. CB1 blockade in vivo significantly attenuated neutrophil infiltration and liver inflammation in CCl4-treated mice. Taken together, CB1 mediates neutrophil chemotaxis and NETosis via Gαi/o/ROS/p38 MAPK signaling pathway in liver inflammation, which represents an effective therapeutic strategy for liver diseases.

scholarly journals Anti-Inflammatory Effect of Geniposide on Osteoarthritis by Suppressing the Activation of p38 MAPK Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yuan Chen ◽  
Kangquan Shou ◽  
Chunlong Gong ◽  
Huarui Yang ◽  
Yi Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Interleukin 1 ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
No Production ◽  
Surgically Induced

It has been suggested that the activation of the p38 mitogen activated protein kinases (MAPKs) signaling pathway plays a significant role in the progression of OA by leading to the overexpression of proinflammatory cytokines, chemokines, and signaling enzymes in human osteoarthritis chondrocytes. However, most p38 MAPK inhibitors applied for OA have been thought to be limited due to their potential long-term toxicities. Geniposide (GE), an iridoid glycoside purified from the fruit of the herb, has been widely used in traditional medicine for the treatment of a variety of chronic inflammatory diseases. In this study, we evaluated the inhibition effect of geniposide on the inflammatory progression of the surgically induced osteoarthritis and whether the protective effect of geniposide on OA is related to the inhibition of the p38 MAPK signaling pathway.In vitro, geniposide attenuated the expression of inflammatory cytokines including interleukin-1 (IL-1), tumor necrosis factor (TNF-α), and nitric oxide (NO) production as well as matrix metalloproteinase- (MMP-) 13 in chondrocytes isolated from surgically induced rabbit osteoarthritis model. Additionally, geniposide markedly suppressed the expression of IL-1, TNF-α, NO, and MMP-13 in the synovial fluid from the rabbits with osteoarthritis. More importantly, our results clearly demonstrated that the inhibitory effect of geniposide on surgery-induced expression of inflammatory mediators in osteoarthritis was closely associated with the suppression of the p38 MAPK signaling pathways. Our study demonstrates that geniposide may have therapeutic potential to serve as an alternative agent for the p38 MAPK inhibition for the treatment of OA due to its inherent features of biological activities and low toxicity as a traditional Chinese medicine.

scholarly journals LncRNA CCAT1 Enhances Chemoresistance in Hepatocellular Carcinoma by Targeting QKI-5

2020 ◽  
Author(s):  
Jing Shi ◽  
Cao Guo ◽  
Junli Ma
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Tumor Model ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Promising Alternative

Abstract Background: A major reason for treatment failure of cancer is acquisition of drug resistance. The specific mechanisms underlying hepatocellular carcinoma (HCC) chemoresistance need to be fully elucidated. lncRNAs involve in drug resistance in some cancers, however, the exact functions of lncRNA colon cancer-associated transcript 1 (CCAT1) in oxaliplatin resistance in HCC need to be elucidated.Methods: Functional analysis of CCAT1 on oxaliplatin sensitivity was performed in HCC cell lines HCCLM3 and HepG2, and in a subcutaneous tumor model receiving OXA treatment. Furthermore, the downstream signaling targets of CCAT1 in HCC were explored. Results: CCAT1 promoted HCC proliferation and reduced the apoptosis induced by oxaliplatin. Knockout of CCAT1 could increased chemosensitivity in vitro and in vivo. Further study found that QKI-5 was an important mediator and blocking of QKI-5/p38 MAPK signaling pathway enhanced oxaliplatin sensitivity.Conclusions: CCAT1 promoted proliferation and oxaliplatin resistance by QKI-5/p38 MAPK signaling pathway in HCC. Targeting CCAT1 in combination with chemotherapeutics may be a promising alternative to reverse drug resistance in HCC treatment.

scholarly journals Attenuation of High Glucose-Induced Damage in RPE Cells through p38 MAPK Signaling Pathway Inhibition

2021 ◽  
Vol 12 ◽  
Author(s):  
Grazia Maugeri ◽  
Claudio Bucolo ◽  
Filippo Drago ◽  
Settimio Rossi ◽  
Michelino Di Rosa ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
High Glucose ◽  
Retinal Pigment ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Rpe Cells ◽  
Cox 2

This study aimed to investigate the high glucose damage on human retinal pigment epithelial (RPE) cells, the role of p38 MAPK signaling pathway and how dimethyl fumarate can regulate that. We carried out in vitro studies on ARPE-19 cells exposed to physiological and high glucose (HG) conditions, to evaluate the effects of DMF on cell viability, apoptosis, and expression of inflammatory and angiogenic biomarkers such as COX-2, iNOS, IL-1β, and VEGF. Our data have demonstrated that DMF treatment attenuated HG-induced apoptosis, as confirmed by reduction of BAX/Bcl-2 ratio. Furthermore, in RPE cells exposed to HG we observed a significant increase of iNOS, COX-2, and IL-1β expression, that was reverted by DMF treatment. Moreover, DMF reduced the VEGF levels elicited by HG, inhibiting p38 MAPK signaling pathway. The present study demonstrated that DMF provides a remarkable protection against high glucose-induced damage in RPE cells through p38 MAPK inhibition and the subsequent down-regulation of VEGF levels, suggesting that DMF is a small molecule that represents a good candidate for diabetic retinopathy treatment and warrants further in vivo and clinical evaluation.

Involvement of the p38 MAPK signaling pathway in S-phase cell-cycle arrest induced by Furazolidone in human hepatoma G2 cells

2012 ◽  
Vol 33 (12) ◽  
pp. 1500-1505 ◽  
Author(s):  
Yu Sun ◽  
Shusheng Tang ◽  
Xi Jin ◽  
Chaoming Zhang ◽  
Wenxia Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
S Phase ◽  
Mapk Signaling Pathway ◽  
Phase Cell ◽  
Human Hepatoma ◽  
Cycle Arrest

scholarly journals Bu Shen Zhu Yun Decoction Improves Endometrial Receptivity via VEGFR-2-Mediated Angiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Li Li ◽  
Huabo Jiang ◽  
Xuecong Wei ◽  
Dandan Geng ◽  
Ming He ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Embryo Implantation ◽  
Mapk Signaling ◽  
Endometrial Receptivity ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Vitro Fertilization

Vascular endothelial growth factor receptor-2 (VEGFR-2) regulates the mitogen-activated protein kinase (MAPK) signaling pathway and plays an important role in angiogenesis. Bu Shen Zhu Yun decoction (BSZYD) can improve endometrial receptivity and embryo implantation rates in patients undergoing in vitro fertilization. However, whether BSZYD improves endometrial receptivity via angiogenesis remains unclear. Here, we investigated the effects of BSZYD on the proliferation, migration, and angiogenesis of human endometrial microvascular endothelial cells (HEMECs) and found that BSZYD upregulated the expression of cyclin D1, matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (PCNA) in HEMECs. Cell Counting Kit 8 assay, scratch-wound assay, and Tube Formation Assay results showed that BSZYD promoted the proliferation, migration, and angiogenesis of HEMECs. Western blot analysis results revealed the activation of the MAPK signaling pathway by BSZYD through the upregulation of VEGF and VEGFR-2 expression. Together, these findings highlight the novel mechanism underlying BSZYD-mediated improvement in endometrial receptivity through the MAPK signaling pathway.

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