scholarly journals Osthole Attenuates Macrophage Activation in Experimental Asthma by Inhibitingthe NF-ĸB/MIF Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruyi Li ◽  
Peng Song ◽  
Guofang Tang ◽  
Jianghong Wei ◽  
Lizong Rao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Macrophage Activation ◽  
Inflammatory Cells ◽  
Activated Macrophages ◽  
Arginase 1 ◽  
Coumarin Compound ◽  
And Migration ◽  
Cluster Of Differentiation

Inhibition of activated macrophages is an alternative therapeutic strategy for asthma. We investigated whether a coumarin compound, osthole, isolated from Cnidiummonnieri (L.) Cuss, alleviated macrophage activation in vivo and in vitro. Osthole could reduce expression of a marker of activated macrophages, cluster of differentiation (CD)206, in an ovalbumin-challenge model of asthma in mice. Osthole could also inhibit infiltration of inflammatory cells, collagen deposition and production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-ɑ, macrophage migration inhibitory factor (MIF)] in asthmatic mice. In vitro, expression of phosphorylated-IĸBɑ, MIF and M2 cytokines (Ym-1, Fizz-1, arginase-1) in IL-4-induced macrophages decreased upon exposure to the NF-ĸB inhibitor MG-132. In our short hairpin (sh)RNA-MIF-knockdown model, reduced expression of M2 cytokines was detected in the IL-4 + shRNA-MIF group. Osthole could attenuate the proliferation and migration of an IL-4-induced rat alveolar macrophages line (NR8383). Osthole could reduce IL-4-induced translocation of nuclear factor-kappa B (NF-ĸB) in NR8383 cells. Collectively, our results suggest that osthole ameliorates macrophage activation in asthma by suppressing the NF-ĸB/MIF signaling pathway, and might be a potential agent for treating asthma.

scholarly journals Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 1985
Author(s):  
Xiaohe Li ◽  
Ling Ma ◽  
Kai Huang ◽  
Yuli Wei ◽  
Shida Long ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
In Vivo Experiments ◽  
Age Related ◽  
And Migration ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.

Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells

2016 ◽  
Vol 130 (17) ◽  
pp. 1523-1533 ◽  
Author(s):  
Chun-Yin Huang ◽  
An-Chen Chang ◽  
Hsien-Te Chen ◽  
Shih-Wei Wang ◽  
Yuan-Shun Lo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Tube Formation ◽  
Human Chondrosarcoma ◽  
Dependent Protein ◽  
And Migration ◽  
Factor C ◽  
Amp Activated Protein Kinase

Chondrosarcoma is the second most frequently occurring type of bone malignancy characterized by distant metastatic propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumour lymphangiogenesis and lymphatic metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. In recent years, adiponectin has also been indicated as facilitating tumorigenesis, angiogenesis and metastasis. However, the effect of adiponectin on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has remained largely a mystery. In the present study, we have shown a clinical correlation between adiponectin and VEGF-C, as well as tumour stage, in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knock down inhibited lymphangiogenesis in vitro and in vivo. We also found that adiponectin-induced VEGF-C is mediated by the calmodulin-dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK) and p38 signaling pathway. Furthermore, the expression of miR-27b was negatively regulated by adiponectin via the CaMKII, AMPK and p38 cascade. The present study is the first to describe the mechanism of adiponectin-promoted lymphangiogenesis by up-regulating VEGF-C expression in chondrosarcomas. Thus, adiponectin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis.

scholarly journals WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

2020 ◽  
Author(s):  
Zi-Qing Shi ◽  
Zi-Yan Chen ◽  
Yao Han ◽  
Heng-Yan Zhu ◽  
Meng-Dan Lyu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Extracellular Signal ◽  
And Migration

Abstract Background: Wnt-inducible signaling pathway protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on the proliferation and migration of ovarian cancer cells in vitro and in vivo.Results: Immunohistochemistry and western blotting indicated that WISP2 was highly expressed in various ovarian cancer tissues and cell lines，but weakly expressed in normal ovary tissue. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells while promoting cell apoptosis and affecting the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of phosphorylated extracellular signal-related kinase (p-ERK)1/2, as well as CCAAT/enhancer-binding protein α (CEBPα) and CEPBβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP).Conclusion: WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

scholarly journals CELL-MEDIATED IMMUNITY AGAINST BESNOITIA AND TOXOPLASMA IN SPECIFICALLY AND CROSS-IMMUNIZED HAMSTERS AND IN CULTURES

1974 ◽  
Vol 139 (3) ◽  
pp. 560-580 ◽  
Author(s):  
Richard L. Hoff ◽  
J. K. Frenkel
Keyword(s):  
Macrophage Activation ◽  
Cell Formation ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Cell Mediated Immunity ◽  
Activated Macrophages ◽  
Specific Effects ◽  
Giant Cell Formation

The capacity of hamster peritoneal cell populations to control viability and growth of Besnoitia and Toxoplasma organisms was assessed in vivo and in vitro. Immunized hamsters reduced the homologous organisms 100- to 10,000-fold over a 5-day period, but the heterologous infection increased 100- to 1,000-fold in numbers, similar as in the nonimmune controls. Passively administered antibody was ineffective although lytic cofactors were supplied by hamsters. In cultures, peritoneal cells from Besnoitia-immune hamsters delayed the growth of homologous parasites to an average of 38.5 h per division; however, in Toxoplasma-immune and nonimmune cells, Besnoitia divided every 12.8 h. Specificity of immunity was pronounced against both infections. With cross-infections, Toxoplasma-immune cultures did not effectively delay Besnoitia growth; however, Besnoitia-immune cultures reduced Toxoplasma growth by one-half. Co-cultivation experiments demonstrated that specifically committed lymphocytes could instruct macrophages to reduce the homologous organism 10-fold, whereas heterologous organisms were reduced only 2-fold. Lymphocyte supernatants initiated hypersensitivity as indicated by macrophage activation and giant cell formation in culture. However, these supernatants did not transfer infection immunity. Lymphokines could account for the hypersensitivity phenomena, but cell-mediated infection immunity in this model required close lymphocyte-macrophage proximity. These studies indicate that a number of distinct processes including delayed hypersensitivity, macrophage activation, and specific cellular immunity are acting simultaneously during latent Besnoitia infection of hamsters. All three processes are mediated by lymphoid cells and appear to be specifically induced. Although activated macrophages develop some heightened nonspecific capabilities, these were several orders of magnitude below the specific effects.

scholarly journals Regulation of arachidonic acid metabolism by macrophage activation.

1982 ◽  
Vol 155 (4) ◽  
pp. 1148-1160 ◽  
Author(s):  
W A Scott ◽  
N A Pawlowski ◽  
H W Murray ◽  
M Andreach ◽  
J Zrike ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Macrophage Activation ◽  
Peritoneal Macrophages ◽  
Arachidonic Acid Metabolism ◽  
Prostaglandin Synthesis ◽  
Activated Macrophages ◽  
Synthetic Enzymes ◽  
Oxygenated Products

Levels of zymosan-induced arachidonic acid (20:4) metabolism by peritoneal macrophages elicited with inflammatory agents and resident macrophages were similar. Thyioglycollate (THIO)-elicited macrophages represented the exception; however, the diminished metabolism by these cells was reproduced by exposing resident cells to 5 mg/ml THIO broth in vitro. In contrast, reduced prostaglandin synthesis by macrophages from mice variously treated with the immunologic agents, Corynebacterium parvum or Bacille Calmette Guérin (BCG), closely correlated with enhanced antitoxoplasma activity, one measure of macrophage activation. This relationship, although not causative, suggested that the capacity for 20:4 metabolism is a function of the macrophage activation state. Modulation of macrophage 20:4 metabolism in vivo apparently required factors in addition to lymphocyte-derived products. Treatment of resident macrophages in vitro with BCG lymphokine was without effect on 20:4 release or prostaglandin synthesis. Activated macrophages from animals inoculated i.p. with C. parvum exhibited reduced 20:4 release and also failed to metabolize 70% of the 20:4 released in response to a zymosan stimulus. Consequently, the quantities of 20:4 metabolites formed were significantly less than expected from 20:4 release. These activated macrophages displayed greatly reduced synthesis of prostacylcin and leukotriene C compared with other 20:4 metabolites. It appeared that factors that regulate macrophage 20:4 metabolism influence the level of the inducible phospholipase and synthetic enzymes for specific 20:4 oxygenated products.

scholarly journals ROCK1 functions as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability

Blood ◽  
2010 ◽  
Vol 115 (9) ◽  
pp. 1785-1796 ◽  
Author(s):  
Sasidhar Vemula ◽  
Jianjian Shi ◽  
Philip Hanneman ◽  
Lei Wei ◽  
Reuben Kapur
Keyword(s):  
Inflammatory Cells ◽  
Receptor Activation ◽  
Normal Expression ◽  
And Migration ◽  
Gsk 3Β ◽  
Migration Of Macrophages ◽  
Rho Kinases ◽  
Rock Activity

Abstract Rho kinases belong to a family of serine/threonine kinases whose role in recruitment and migration of inflammatory cells is poorly understood. We show that deficiency of ROCK1 results in increased recruitment and migration of macrophages and neutrophils in vitro and in vivo. Enhanced migration resulting from ROCK1 deficiency is observed despite normal expression of ROCK2 and a significant reduction in overall ROCK activity. ROCK1 directly binds PTEN in response to receptor activation and is essential for PTEN phosphorylation and stability. In the absence of ROCK1, PTEN phosphorylation, stability, and its activity are significantly impaired. Consequently, increased activation of downstream targets of PTEN, including PIP3, AKT, GSK-3β, and cyclin D1, is observed. Our results reveal ROCK1 as a physiologic regulator of PTEN whose function is to repress excessive recruitment of macrophages and neutrophils during acute inflammation.

Cinobufacini Inhibits Colon Cancer Invasion and Metastasis via Suppressing Wnt/β-Catenin Signaling Pathway and EMT

2020 ◽  
Vol 48 (03) ◽  
pp. 703-718 ◽  
Author(s):  
Jie Wang ◽  
Han Cai ◽  
Qiaoli Liu ◽  
Yue Xia ◽  
LiKai Xing ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
Cancer Invasion ◽  
In Vivo Studies ◽  
Colon Cancer Cells ◽  
Invasion And Metastasis ◽  
Invasion And Migration ◽  
And Migration

Cinobufacini is a well-known Chinese medicine extracted from Venenum Bufonis, also called Chan Su. It has been used clinically for various cancers, including colon cancer. However, the function of Cinobufacini on colon cancer invasion and metastasis, and its underlying molecular mechanism, is still not clear. In this study, we investigated the function and mechanism of Cinobufacini on colon cancer invasion and metastasis both in vitro and in vivo studies. Human colon cancer cells were cultured. CCK assay was used to detect the effect of Cinobufacini on colon cancer cells proliferation. The invasion and migration abilities were observed by transwell assays, and the expression of invasion and migration related genes MMP2, MMP9, and epithelial-to-mesenchymal transition (EMT) relate genes were observed by Western blot assays. An orthotopic xenograft model in nude mice was established using colon cancer HCT116 cells, and the function of Cinobufacini on colon cancer invasion and metastasis were observed in vivo. We found Cinobufacini significantly inhibited colon cancer cell proliferation in a dose/time-dependent manner; the invasion and migration abilities of colon cancer were decreased after treated with Cinobufacini. The metastasis and EMT related genes MMP9, MMP2, N-cadherin and Snail were obviously down-regulated, while the expression of E-cadherin was up-regulated after treatment with Cinobufacini. The Wnt/[Formula: see text]-catenin signaling pathway related genes were observed using WB,and results show that the expression of [Formula: see text]-catenin, wnt3a, c-myc, cyclin D1, and MMP7 were all down-regulated after being treated with cinobufacini, while the expression of APC was up-regulated. In vivo studies of the volume and weight of orthotopic xenograft tumors showed significantly shrinkage in the Cinobufacini group compared to the control group. The enterocoelia and liver metastasis tumors were significantly decreased, and the expression of MMP9, MMP2, and [Formula: see text]-catenin were also down-regulated, while E-cadherin was up-regulated in vivo after the treatment with Cinobufacini. Our data proves that Cinobufacini can inhibit colon cancer invasion and metastasis both in vitro and in vivo; the mechanism is related by suppressing the Wnt/[Formula: see text]-catenin signaling pathway and then inhibiting the EMT of CRC.

scholarly journals Erratum

2021 ◽  
Vol 28 (6) ◽  
pp. 681-682
Author(s):  
Juan Gu ◽  
Chang-fu Cui ◽  
Li Yang ◽  
Ling Wang ◽  
Xue-hua Jiang
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Mrna Level ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Invasion And Migration ◽  
Downstream Target ◽  
And Migration

Colon cancer (CC) is the third most common cancer worldwide. Emodin is an anthraquinone-active substance that has the ability to affect tumor progression. Our study aims to explore the effects and the relevant mechanism of emodin on the invasion and migration of CC in vitro and in vivo. In our study, we found that emodin inhibited the invasion and migration abilities of RKO cells and decreased the expression of matrix metalloproteinase-7 (MMP-7), MMP-9, and vascular endothelial growth factor (VEGF) in a dose-dependent manner. Further research suggested that emodin inhibited EMT by increasing the mRNA level of E-cadherin and decreasing the expression of N-cadherin, Snail, and -catenin. Emodin also significantly inhibited the activation of the Wnt/-catenin signaling pathway by downregulating the expression of related downstream target genes, including TCF4, cyclin D1, and c-Myc. A Wnt/-catenin signaling pathway agonist abolished the effect of emodin on EMT and cell mobility, suggesting that emodin exerted its regulating role through the Wnt/-catenin pathway. The CC xenograft model was established to study the antitumor efficiency of emodin in vivo. The in vivo study further demonstrated that emodin (40 mg/kg) suppressed tumor growth by inhibiting EMT via the Wnt/-catenin signaling pathway in vivo. Taken together, we suggest that emodin inhibits the invasion and migration of CC cells in vitro and in vivo by blocking EMT, which is related with the inhibition of the Wnt/-catenin signaling pathway.

scholarly journals Myo1e modulates the recruitment of B cells to inguinal lymph nodes

2019 ◽  
Author(s):  
Daniel Alberto Girón-Pérez ◽  
Eduardo Vadillo ◽  
Michael Schnoor ◽  
Leopoldo Santos-Argumedo
Keyword(s):  
Cell Migration ◽  
B Cells ◽  
Lymph Nodes ◽  
Signaling Pathway ◽  
High Endothelial Venules ◽  
Long Tail ◽  
Summary Statement ◽  
And Migration

AbstractThe recruitment of leukocyte to high endothelium venules and their migration to the lymph nodes are critical steps to initiate an immune response. Cell migration is regulated by the actin cytoskeleton where myosins have a very import role. Myo1e is a long tail class I myosin highly expressed in B cells that not have been studied in the context of cell migration. By using an in vivo model, through the use of intravital microscopy, we demonstrated the relevance of Myo1e in the adhesion and the migration of B cells in high endothelial venules. These observations were confirmed by in vitro experiments. We also registered a reduction in the expression of integrins and F-actin in the protrusion of B lymphocytes membrane. Deficiencies in vesicular trafficking can explain the decrease of integrins on the surface. Interestingly, Myo1e is associated with focal adhesion kinase (FAK). The lack of Myo1e affected the phosphorylation of FAK and AKT, and the activity of RAC-1, disturbing the FAK/PI3K/RAC-1 signaling pathway. Together, our results indicate critical participation of Myo1e in the mechanism of B cell migration.Summary statementMyo1e participate in the adhesion and migration in the high endothelial venules by regulation of integrins and the PI3K/FAK/RAC-1 signaling pathway.

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