17β-estradiol induces CD40 expression in dendritic cells via MAPK signaling pathways in a minichromosome maintenance protein 6-dependent manner

AbstractSubacute ruminal acidosis (SARA) can increase the level of inflammation and induce rumenitis in dairy cows. Berberine (BBR) is the major active component of Rhizoma Coptidis, which is a type of Chinese anti-inflammatory drug for gastrointestinal diseases. The purpose of this study was to investigate the anti-inflammatory effects of BBR on lipopolysaccharide (LPS)-stimulated rumen epithelial cells (REC) and the underlying molecular mechanisms. REC were cultured and stimulated with LPS in the presence or absence of different concentrations of BBR. The results showed that cell viability was not affected by BBR. Moreover, BBR markedly decreased the concentrations and mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the LPS-treated REC in a dose-dependent manner. Importantly, Western blotting analysis showed that BBR significantly suppressed the protein expression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein (MyD88) and the phosphorylation of nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) in LPS-treated REC. Furthermore, the results of immunocytofluorescence showed that BBR significantly inhibited the nuclear translocation of NF-κB p65 induced by LPS treatment. In conclusion, the protective effects of BBR on LPS-induced inflammatory responses in REC may be due to its ability to suppress the TLR4-mediated NF-κB and MAPK signaling pathways. These findings suggest that BBR can be used as an anti-inflammatory drug to treat inflammation induced by SARA.

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MAPK signaling pathways are needed for survival of H9c2 cardiac myoblasts under extracellular alkalosis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01362.2007 ◽

2008 ◽

Vol 295 (3) ◽

pp. H1319-H1329 ◽

Cited By ~ 10

Author(s):

Konstantina Stathopoulou ◽

Isidoros Beis ◽

Catherine Gaitanaki

Keyword(s):

Signaling Pathways ◽

P38 Mapk ◽

Cardiac Myocyte ◽

Consensus Sequence ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Dependent Manner ◽

Selective Inhibitors ◽

Cardiac Myoblasts ◽

Mapk Signaling Pathways

pH is one of the most important physiological parameters, with its changes affecting the function of vital organs like the heart. However, the effects of alkalosis on the regulation of cardiac myocyte function have not been extensively investigated. Therefore, we decided to study whether the mitogen-activated protein kinase (MAPK) signaling pathways [c-Jun NH2-terminal kinases (JNKs), extracellular signal-regulated kinases (ERKs), and p38 MAPK] are activated by alkalosis induced with Tris-Tyrode buffer at two pH values, 8.5 and 9.5, in H9c2 rat cardiac myoblasts. These buffers also induced intracellular alkalinization comparable to that induced by 1 mM NH4Cl. The three MAPKs examined presented differential phosphorylation patterns that depended on the severity and the duration of the stimulus. Inhibition of Na+/H+ exchanger (NHE)1 by its inhibitor HOE-642 prevented alkalinization and partially attenuated the alkalosis (pH 8.5)-induced activation of these kinases. The same stimulus also promoted c-Jun phosphorylation and enhanced the binding at oligonucleotides bearing the activator protein-1 (AP-1) consensus sequence, all in a JNK-dependent manner. Additionally, mitogen- and stress-activated kinase 1 (MSK1) was transiently phosphorylated by alkalosis (pH 8.5), and this was abolished by the selective inhibitors of either p38 MAPK or ERK pathways. JNKs also mediated Bcl-2 phosphorylation in response to incubation with the alkaline medium (pH 8.5), while selective inhibitors of the three MAPKs diminished cell viability under these conditions. All these data suggest that alkalosis activates MAPKs in H9c2 cells and these kinases, in turn, modify proteins that regulate gene transcription and cell survival.

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An Inhibitory Role of Osthole in Rat MSCs Osteogenic Differentiation and Proliferation via Wnt/β-Catenin and Erk1/2-MAPK Pathways

Cellular Physiology and Biochemistry ◽

10.1159/000445590 ◽

2016 ◽

Vol 38 (6) ◽

pp. 2375-2388 ◽

Cited By ~ 12

Author(s):

Hongyang Hu ◽

Min Chen ◽

Guangzu Dai ◽

Guoqing Du ◽

Xuezong Wang ◽

...

Keyword(s):

Osteogenic Differentiation ◽

Signaling Pathways ◽

Western Blotting ◽

Underlying Mechanism ◽

Mapk Signaling ◽

Cell Counting ◽

Nuclear Antigen ◽

Dependent Manner ◽

Alizarin Red ◽

Mapk Signaling Pathways

Background/Aims: Bone marrow-derived mesenchymal stem cells (MSCs) are responsible for new bone formation during adulthood. Accumulating evidences showed that Osthole promotes the osteogenic differentiation in primary osteoblasts. The aim of this study was to investigate whether Osthole exhibits a potential to stimulate the osteogenic differentiation of MSCs and the underlying mechanism. Methods: MSCs were treated with a gradient concentration of Osthole (6.25 µM, 12.5 µM, and 25 µM). Cell proliferation was assessed by western blotting with the proliferating cell nuclear antigen (PCNA) and Cyclin D1 antibodies, fluorescence activated cell sorting (FACS), and cell counting kit 8 (CCK8). MSCs were cultured in osteogenesis-induced medium for one or two weeks. The osteogenic differentiation of MSCs was estimated by Alkaline Phosphatase (ALP) staining, Alizarin red staining, Calcium influx, and quantitative PCR (qPCR). The underlying mechanism of Osthole-induced osteogenesis was further evaluated by western blotting with antibodies in Wnt/β-catenin, PI3K/Akt, BMPs/smad1/5/8, and MAPK signaling pathways. Results: Osthole inhibited proliferation of rat MSCs in a dose-dependent manner. Osthole suppressed osteogenic differentiation of rat MSCs by down-regulating the activities of Wnt/β-catenin and Erk1/2-MAPK signaling. Conclusions: Osthole inhibits the proliferation and osteogenic differentiation of rat MSCs, which might be mediated through blocking the Wnt/β-catenin and Erk1/2-MAPK signaling pathways.

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Urocortins exhibit differential effects on PGE2 and PGF2α output via CRHR2 in human myometrium

Reproduction ◽

10.1530/rep-20-0659 ◽

2021 ◽

Author(s):

Xingji You ◽

Zixi Chen ◽

Qianqian Sun ◽

Ruojing Yao ◽

Hang Gu ◽

...

Keyword(s):

Signaling Pathways ◽

Mapk Signaling ◽

Human Myometrium ◽

Dependent Manner ◽

Camp Production ◽

Inflammatory Stimuli ◽

Crh Receptor Type 1 ◽

Dose Dependent ◽

Mapk Signaling Pathways

Urocortins (UCNs), belonging to corticotropin-releasing hormone (CRH) family, exert their function via CRH receptor type 1(CRHR1) and 2 (CRHR2). Our previous studies have demonstrated that CRH acts on CRHR1 to potentiate prostaglandin (PG) output induced by inflammatory stimuli in myometrial cells. In the present study, we sought to investigate the effects of UCNs on prostaglandin (PG) output via CRHR2 in cultured human uterine smooth muscle cells (HUSMCs) from human term myometrium. We found that UCN and UCN3 treatment promoted PGE2 and PGF2α secretion in a dose-dependent manner. In contrast, UCN2 dose-dependently inhibited PGE2 and PGF2α secretion. Their effects could be reversed by CRHR2 antagonist and CRHR2 siRNA. Mechanically, we showed that UCN and UCN3 suppressed cAMP production and led to Gi activation, while UCN2 promoted cAMP production and activated Gs signaling. Further, UCN and UCN3 could activate NF-κB and MAPK signaling pathways. These effects were dependent on Gi signaling. In contrast, UCN did not activate MAPK and NF-κB signaling. UCN and UCN3 stimulation of PG secretion was dependent on Gi/adenylyl cyclase (AC)/cAMP, NF-κB and MAPK signaling pathways, while UCN2 suppression of PG output was through Gs/AC/cAMP signaling pathways. Our data suggest that UCN, UCN2 and UCN3 can finely regulate the secretion of PGs via CRHR2, which facilities the functional status of uterus during pregnancy.

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Immune activation of murine RAW264.7 macrophages by sonicated and alkalized paramylon from Euglena gracilis

BMC Microbiology ◽

10.1186/s12866-020-01782-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Qingqing Guo ◽

Decheng Bi ◽

Mingcan Wu ◽

Boming Yu ◽

Lang Hu ◽

...

Keyword(s):

Nitric Oxide ◽

Immune System ◽

Signaling Pathways ◽

Euglena Gracilis ◽

Mapk Signaling ◽

Regulation Mechanism ◽

Dependent Manner ◽

Raw264.7 Macrophages ◽

Therapeutic Benefits ◽

Mapk Signaling Pathways

Abstract Background Euglena is a new super health food resource that is rich in the natural polysaccharide paramylon, a linear β-1,3-glucan with various biological activities including activity on the immune system in different cell lines and animals. Despite these reports, the immune regulation mechanism of paramylon is still unclear. Results We investigate the signaling pathways paramylon impacts in immune macrophages. In RAW264.7 macrophages, sonicated and alkalized paramylon oligomers up-regulated inducible nitric oxide synthase (iNOS) and increased secretion of nitric oxide (NO), interleukin (IL)-6 and tumor necrosis factor (TNF)-α, in a concentration-dependent manner. In addition, paramylon activated the nuclear factor-κB(NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and inhibiting these pathways attenuated the paramylon-induced secretion of the above immune-mediators. Conclusions These results demonstrate that Euglena gracilis paramylon modulates the immune system via activation of the NF-κB and MAPK signaling pathways and thus has potential therapeutic benefits.

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The Coumarin Derivative 5′-Hydroxy Auraptene Suppresses Osteoclast Differentiation via Inhibiting MAPK and c-Fos/NFATc1 Pathways

BioMed Research International ◽

10.1155/2019/9395146 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Basem M. Abdallah ◽

Enas M. Ali ◽

Hany Elsawy ◽

Gehan M. Badr ◽

Ashraf M. Abdel-Moneim ◽

...

Keyword(s):

Signaling Pathways ◽

Gene Expression Regulation ◽

Osteoclast Differentiation ◽

Coumarin Derivative ◽

Mapk Signaling ◽

Tartrate Resistant Acid Phosphatase ◽

Mouse Bone Marrow ◽

Dependent Manner ◽

Dose Dependent ◽

Mapk Signaling Pathways

The phytochemical substances, coumarin derivatives, have demonstrated antiresorptive bone effects by suppressing osteoclast differentiation in vitro and in vivo. Recently, we have identified 5′-hydroxy auraptene (5′-HA), a coumarin derivative isolated from Lotus lalambensis Schweinf, as a novel stimulator for osteoblast differentiation. In this study, we investigated the effect of 5′-HA on osteoclast differentiation of mouse bone marrow (BM) cells. The effect of 5′-HA on BM cell proliferation and osteoclast differentiation was determined by measuring cell viability and tartrate-resistant acid phosphatase (TRAP) enzyme activity, quantification of TRAP+ multinucleated cells (TRAP+MNCs), and quantitative real-time PCR (qPCR) of osteoclastic gene expression. Regulation of NF-κB, c-Fos/NFATc1, and MAPK signaling pathways by 5′-HA during osteoclastogenesis was measured by the NF-κB reporter assay and Western blot analysis. 5′-HA significantly suppresses the receptor activator of NF-κB ligand (RANKL) induced osteoclast differentiation of BM cells in a dose-dependent manner. Consistently, treatment of BM cells with 5′-HA significantly inhibited RANKL-induced activation of NF-κB and c-Fos/NFATc1 pathways in a dose-dependent manner. Furthermore, RANKL-induced phosphorylation of ERK1/2, p-38, and JNK was significantly inhibited by 5′-HA in BM cells. In conclusion, we identified 5′-HA as a novel coumarin derivative that suppresses RANKL-induced osteoclastogenesis via inhibiting c-Fos/NFATc1 and MAPK signaling pathways.

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Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-κB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner

Cell Death and Differentiation ◽

10.1038/sj.cdd.4401996 ◽

2006 ◽

Vol 14 (2) ◽

pp. 306-317 ◽

Cited By ~ 82

Author(s):

L Wang ◽

W-L Zhao ◽

J-S Yan ◽

P Liu ◽

H-P Sun ◽

...

Keyword(s):

Signaling Pathways ◽

Caspase 3 ◽

Mapk Signaling ◽

Leukemia Cells ◽

Dependent Manner ◽

Eriocalyxin B ◽

Mapk Signaling Pathways

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Immune activation of murine RAW264.7 macrophages by sonicated and alkalized paramylon from Euglena gracilis

10.21203/rs.2.18242/v4 ◽

2020 ◽

Author(s):

Qingqing Guo ◽

Decheng Bi ◽

Mingcan Wu ◽

Boming Yu ◽

Lang Hu ◽

...

Keyword(s):

Nitric Oxide ◽

Immune System ◽

Signaling Pathways ◽

Euglena Gracilis ◽

Mapk Signaling ◽

Regulation Mechanism ◽

Dependent Manner ◽

Raw264.7 Macrophages ◽

Therapeutic Benefits ◽

Mapk Signaling Pathways

Abstract Background: Euglena is a new super health food resource that is rich in the natural polysaccharide paramylon, a linear β-1,3-glucan with various biological activities including activity on the immune system in different cell lines and animals. Despite these reports, the immune regulation mechanism of paramylon is still unclear. Results: We investigate the signaling pathways paramylon impacts in immune macrophages. In RAW264.7 macrophages, sonicated and alkalized paramylon oligomers up-regulated inducible nitric oxide synthase (iNOS) and increased secretion of nitric oxide (NO), interleukin (IL)-6 and tumor necrosis factor (TNF)-α, in a concentration-dependent manner. In addition, paramylon activated the nuclear factor-κB(NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and inhibiting these pathways attenuated the paramylon-induced secretion of the above immune-mediators. Conclusions: These results demonstrate that Euglena gracilis paramylon modulates the immune system via activation of the NF-κB and MAPK signaling pathways and thus has potential therapeutic benefits.

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Wharton Jelly Stem Cells inhibits AGS Gastric Cancer Cells through Induction of Apoptosis and Modification of MAPK and NF‑κB Signaling Pathways

10.21203/rs.3.rs-142543/v1 ◽

2021 ◽

Author(s):

Samaneh Abbasi ◽

Reza Bazyar ◽

Mohammad Ali Saremi ◽

Gholamhoseen Alishiri ◽

Nasrin Seyyedsani ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Mrna Expression ◽

Cancer Cells ◽

Signaling Pathways ◽

Cell Line ◽

Mapk Signaling ◽

Dependent Manner ◽

Induction Of Apoptosis ◽

Mapk Signaling Pathways

Abstract Background and aim: Gastric cancer) GC) is one of the most common cancer with high mortality worldwide. The human Wharton's jelly stem cells (hWJSCs) can inhibit several cancer cells through several molecular pathways. Therefore, the present study aimed to investigate anticancer effects of hWJSCs conditioned medium (hWJSC-CM) and cell-free lysate (hWJSC-CL) against of GC cell line AGS and underlying signaling pathways. Methods: In this study, we evaluated the effects of hWJSC-CM and hWJSC-CL on viability, proliferation, migration, invasion, apoptosis, and MAPK and NF‑κB signaling pathways in AGS cells. Moreover, mRNA expression of genes involved in apoptosis (BAX, BCL2, SMAC, and SURVIVIN), as well as expression of proteins involved in NF-κB and MAPK signaling pathways were evaluated. Results: The obtained results showed that the hWJSC-CM and hWJSC-CL decreased viability, migration, and invasion of GC cell line AGS in a concentration and time dependent manner. We observed that the hWJSC-CM and hWJSC-CL induced apoptosis pathway through regulation of apoptosis involved genes mRNA expression. In addition, the hWJSC-CM and hWJSC-CL suppressed NF-κB signaling pathways as well as promoted MAPK signaling pathways. Conclusions: In general, our study suggested that the hWJSC-CM and hWJSC-CL inhibits proliferation and viability of GC cell line AGS through induction of apoptosis, as well as modification of NF-κB and MAPK signaling pathways.

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Immune activation of murine RAW264.7 macrophages by sonicated and alkalized paramylon from Euglena gracilis

10.21203/rs.2.18242/v1 ◽

2019 ◽

Author(s):

Qingqing Guo ◽

Decheng Bi ◽

Mingcan Wu ◽

Boming Yu ◽

Lang Hu ◽

...

Keyword(s):

Nitric Oxide ◽

Immune System ◽

Signaling Pathways ◽

Euglena Gracilis ◽

Mapk Signaling ◽

Regulation Mechanism ◽

Dependent Manner ◽

Raw264.7 Macrophages ◽

Therapeutic Benefits ◽

Mapk Signaling Pathways

Abstract Background: Euglena as a new super health food resource that is rich in the natural polysaccharide paramylon, a linear β-1,3-glucan with various biological activities including activity on the immune system in different cell lines and animals. Despite these reports, the immune regulation mechanism of paramylon is still unclear. Results: We investigate the signaling pathways paramylon impacts in immune macrophages. In RAW264.f:7 macrophages, sonicated and alkalized paramylon oligomers up-regulated inducible nitric oxide synthase (iNOS) and increased secretion of nitric oxide (NO), interleukin (IL)-6 and tumor necrosis factor (TNF)-α, in a concentration-dependent manner. In addition, paramylon activated the nuclear factor-κB(NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and inhibiting these pathways attenuated the paramylon-induced secretion of the above immune-mediators. Conclusions: These results demonstrate that Euglena gracilis paramylon modulates the immune system via activation of the NF-κB and MAPK signaling pathways and thus has potential therapeutic benefits.

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