scholarly journals Dexamethasone enhances CD163 expression in porcine IPKM immortalized macrophages

2021 ◽  
Vol 57 (1) ◽  
pp. 10-16
Author(s):  
Takato Takenouchi ◽  
Takeya Morozumi ◽  
Emi Wada ◽  
Shunichi Suzuki ◽  
Yasutaka Nishiyama ◽  
...  
Keyword(s):  
Scavenger Receptor ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Respiratory Syndrome Virus ◽  
Phenotypic Marker ◽  
Putative Receptor ◽  
Cd163 Expression ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

AbstractIn our previous study, we established a unique porcine macrophage cell line, immortalized porcine kidney-derived macrophages (IPKM). The purpose of the present study was to further elucidate the characteristics of IPKM. CD163 is a scavenger receptor for the hemoglobin-haptoglobin complex and is used as a phenotypic marker of anti-inflammatory M2 macrophages. The expression of CD163 is enhanced by dexamethasone (DEX), a potent steroidal anti-inflammatory drug, in human and rodent macrophages in vitro. Therefore, we investigated the effects of DEX on CD163 expression in porcine IPKM. Treatment with DEX markedly enhanced CD163 expression in the IPKM. In addition, we found that SB203580, a selective inhibitor of p38 mitogen-activated protein kinase (MAPK), blocked the effects of DEX, suggesting that the p38 MAPK signaling pathway is involved in the regulation of the DEX-induced enhancement of CD163 expression. Since CD163 is considered to be a putative receptor for the porcine reproductive and respiratory syndrome virus (PRRSV), the effects of DEX on the infection of IPKM by PRRSV were evaluated. Although the IPKM were susceptible to infection by the Fostera PRRSV vaccine strain, DEX treatment did not affect the propagation of the virus in the IPKM. This suggests that the DEX-induced enhancement of CD163 expression alone is not sufficient to facilitate the infection of IPKM by PRRSV.

scholarly journals Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1343
Author(s):  
Balaji Venkataraman ◽  
Saeeda Almarzooqi ◽  
Vishnu Raj ◽  
Abdullah T. Alhassani ◽  
Ahmad S. Alhassani ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Activity Index ◽  
Nigella Sativa ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Ppar Γ ◽  
Anti Inflammatory ◽  
Ht 29

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in Nigella sativa, for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.

scholarly journals Neuroprotective potential of isothiocyanates in an in vitro model of neuroinflammation

2020 ◽  
Author(s):  
Tiziana Latronico ◽  
Marilena Larocca ◽  
Serafina Milella ◽  
Anna Fasano ◽  
Rocco Rossano ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Neurological Diseases ◽  
Primary Cultures ◽  
Allyl Isothiocyanate ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Pcr Analysis ◽  
Ros Production ◽  
Mitogen Activated Protein

AbstractIsothiocyanates (ITCs), present as glucosinolate precursors in cruciferous vegetables, have shown anti-inflammatory, antioxidant and anticarcinogenic activities. Here, we compared the effects of three different ITCs on ROS production and on the expression of matrix metalloproteinase (MMP)-2 and -9, which represent important pathogenetic factors of various neurological diseases. Primary cultures of rat astrocytes were activated by LPS and simultaneously treated with different doses of Allyl isothiocyanate (AITC), 2-Phenethyl isothiocyanate (PEITC) and 2-Sulforaphane (SFN). Results showed that SFN and PEITC were able to counteract ROS production induced by H2O2. The zymographic analysis of cell culture supernatants evidenced that PEITC and SFN were the most effective inhibitors of MMP-9, whereas, only SFN significantly inhibited MMP-2 activity. PCR analysis showed that all the ITCs used significantly inhibited both MMP-2 and MMP-9 expression. The investigation on the mitogen-activated protein kinase (MAPK) signaling pathway demonstrated that ITCs modulate MMP transcription by inhibition of extracellular-regulated protein kinase (ERK) activity. Results of this study suggest that ITCs could be promising nutraceutical agents for the prevention and complementary treatment of neurological diseases associated with MMP involvement.

Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by Inhibiting Mitogen-Activated Protein Kinase Activation

2017 ◽  
Vol 45 (04) ◽  
pp. 847-861 ◽  
Author(s):  
Chia-Yang Li ◽  
Katsuhiko Suzuki ◽  
Yung-Li Hung ◽  
Meng-Syuan Yang ◽  
Chung-Ping Yu ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aloe Vera ◽  
Peritoneal Macrophages ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Raw264.7 Macrophages ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.

scholarly journals Insulin acts via mitogen-activated protein kinase phosphorylation in rabbit blastocysts

Reproduction ◽  
2004 ◽  
Vol 128 (5) ◽  
pp. 517-526 ◽  
Author(s):  
Anne Navarrete Santos ◽  
Sarah Tonack ◽  
Michaela Kirstein ◽  
Marie Pantaleon ◽  
Peter Kaye ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Transport ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Preimplantation Embryos ◽  
Mrna Levels ◽  
Glut4 Translocation ◽  
Mitogen Activated Protein ◽  
Rabbit Embryos

The addition of insulin during in vitro culture has beneficial effects on rabbit preimplantation embryos leading to increased cell proliferation and reduced apoptosis. We have previously described the expression of the insulin receptor (IR) and the insulin-responsive glucose transporters (GLUT) 4 and 8 in rabbit preimplantation embryos. However, the effects of insulin on IR signaling and glucose metabolism have not been investigated in rabbit embryos. In the present study, the effects of 170 nM insulin on IR, GLUT4 and GLUT8 mRNA levels, Akt and Erk phosphorylation, GLUT4 translocation and methyl glucose transport were studied in cultured day 3 to day 6 rabbit embryos. Insulin stimulated phosphorylation of the mitogen-activated protein kinase (MAPK) Erk1/2 and levels of IR and GLUT4 mRNA, but not phosphorylation of the phosphatidylinositol 3-kinase-dependent protein kinase, Akt, GLUT8 mRNA levels, glucose uptake or GLUT4 translocation. Activation of the MAPK signaling pathway in the absence of GLUT4 translocation and of a glucose transport response suggest that in the rabbit preimplantation embryo insulin is acting as a growth factor rather than a component of glucose homeostatic control.

A cross talk between class a scavenger receptor and receptor for advanced glycation end-products contributes to diabetic retinopathy

2014 ◽  
Vol 307 (12) ◽  
pp. E1153-E1165 ◽  
Author(s):  
Ke Ma ◽  
Yiming Xu ◽  
Chenchen Wang ◽  
Nan Li ◽  
Kexue Li ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Protein Kinase ◽  
Cross Talk ◽  
Scavenger Receptor ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Class A ◽  
End Products ◽  
Mitogen Activated Protein ◽  
Class A Scavenger Receptor

In response to hyperglycemia in patients with diabetes, many signaling pathways contribute to the pathogenesis of diabetic complications, including diabetic retinopathy (DR). Excessive production of inflammatory mediators plays an important role in this process. Amadori-glycated albumin, one of the major forms of advanced glycated end-products, has been implicated in DR by inducing inflammatory responses in microglia/macrophages. Our goal was to delineate the potential cross talk between class A scavenger receptor (SR-A) and the receptor for advanced glycated end-product (RAGE) in the context of DR. We show here that SR-A ablation caused an exacerbated form of DR in streptozotocin-injected C57BL/6J mice as evidenced by fundus imaging and electroretinography. Immunohistochemical staining and RT-PCR assay indicated that there was augmented activation of proinflammatory macrophages with upregulated synthesis of proinflammatory mediators in the retina in Sr-a−/− mice. Overexpression of SR-A suppressed RAGE-induced mitogen-activated protein kinase (MAPK) signaling, whereas RAGE activation in macrophages favored a proinflammatory (M1) phenotype in the absence of SR-A. Mechanistic analysis on bone marrow-derived macrophages and HEK293 cell line revealed that SR-A interacted with and inhibited the phosphorylation of mitogen-activated protein kinase kinase 7, the major kinase in the RAGE-MAPK-NF-κB signaling, thereby leading to diminished secretion of proinflammatory cytokines. Our findings suggest that the antagonism between SR-A and RAGE contributes to the pathogenesis of DR by nurturing a disease-prone macrophage phenotype. Therefore, specific agonist that boosts SR-A signaling could potentially provide benefits in the prevention and/or intervention of DR.

scholarly journals Identification of RAS-Mitogen-Activated Protein Kinase Signaling Pathway Modulators in an ERF1 Redistribution® Screen

2006 ◽  
Vol 11 (4) ◽  
pp. 423-434 ◽  
Author(s):  
Charlotta Grånäs ◽  
Betina Kerstin Lundholt ◽  
Frosty Loechel ◽  
Hans-Christian Pedersen ◽  
Sara Petersen Bjørn ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Kinase Inhibitors ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
A Cell ◽  
Protein Kinase Signaling

The RAS-mitogen-activated protein kinase (MAPK) signaling pathway has a central role in regulating the proliferation and survival of both normal and tumor cells. This pathway has been 1 focus area for the development of anticancer drugs, resulting in several compounds, primarily kinase inhibitors, in clinical testing. The authors have undertaken a cell-based, high-throughput screen using a novel ERF1 Redistribution® assay to identify compounds that modulate the signaling pathway. The hit compounds were subsequently tested for activity in a functional cell proliferation assay designed to selectively detect compounds inhibiting the proliferation of MAPK pathway-dependent cancer cells. The authors report the identification of 2 cell membrane-permeable compounds that exhibit activity in the ERF1 Redistribution® assay and selectively inhibit proliferation of MAPK pathway-dependent malignant melanoma cells at similar potencies (IC50 =< 5 μM). These compounds have drug-like structures and are negative in RAF, MEK, and ERK in vitro kinase assays. Drugs belonging to these compound classes may prove useful for treating cancers caused by excessive MAPK pathway signaling. The results also show that cell-based, high-content Redistribution® screens can detect compounds with different modes of action and reveal novel targets in a pathway known to be disease relevant.

Aggravation of ADAMTS and Matrix Metalloproteinase Production and Role of ERK1/2 Pathway in the Interaction of Osteoarthritic Subchondral Bone Osteoblasts and Articular Cartilage Chondrocytes — Possible Pathogenic Role in Osteoarthritis

2012 ◽  
Vol 39 (3) ◽  
pp. 621-634 ◽  
Author(s):  
INDIRA PRASADAM ◽  
ROSS CRAWFORD ◽  
YIN XIAO
Keyword(s):  
Articular Cartilage ◽  
Signaling Pathway ◽  
Subchondral Bone ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Coculture Model ◽  
Degradative Enzymes ◽  
A Disintegrin And Metalloproteinase

Objective.Degradative enzymes, such as A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinases (MMP), play key roles in development of osteoarthritis (OA). We investigated if crosstalk between subchondral bone osteoblasts (SBO) and articular cartilage chondrocytes (ACC) in OA alters the expression and regulation of ADAMTS5, ADAMTS4, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-13, and also tested the possible involvement of mitogen-activated protein kinase (MAPK) signaling pathway during this process.Methods.ACC and SBO were isolated from normal and OA patients. An in vitro coculture model was developed to study the regulation of ADAMTS and MMP under normal and OA joint crosstalk conditions. The MAPK-ERK inhibitor PD98059 was applied to delineate the involvement of specific pathways during this interaction process.Results.Indirect coculture of OA SBO with normal ACC resulted in significantly increased expression of ADAMTS5, ADAMTS4, MMP-2, MMP-3, and MMP-9 in ACC, whereas coculture of OA ACC led to increased MMP-1 and MMP-2 expression in normal SBO. Upregulation of ADAMTS and MMP under these conditions was correlated with activation of the MAPK-ERK1/2 signaling pathway, and addition of the MAPK-ERK inhibitor PD98059 reversed the overexpression of ADAMTS and MMP in cocultures.Conclusion.These results add to the evidence that in human OA, altered bidirectional signals between SBO and ACC significantly influence the critical features of both cartilage and bone by producing abnormal levels of ADAMTS and MMP. We have demonstrated for the first time that this altered crosstalk was mediated by the phosphorylation of MAPK-ERK1/2 signaling pathway.

scholarly journals Mating and Pathogenic Development of the Smut Fungus Ustilago maydis Are Regulated by One Mitogen-Activated Protein Kinase Cascade

2003 ◽  
Vol 2 (6) ◽  
pp. 1187-1199 ◽  
Author(s):  
Philip Müller ◽  
Gerhard Weinzierl ◽  
Andreas Brachmann ◽  
Michael Feldbrügge ◽  
Regine Kahmann
Keyword(s):  
Protein Kinase ◽  
Ustilago Maydis ◽  
Mapk Signaling ◽  
Tube Formation ◽  
Mitogen Activated Protein Kinase ◽  
Phytopathogenic Fungus ◽  
Mapk Kinase ◽  
Mitogen Activated Protein ◽  
Kinase Cascade

ABSTRACT In the phytopathogenic fungus Ustilago maydis, pheromone-mediated cell fusion is a prerequisite for the generation of the infectious dikaryon. The pheromone signal elevates transcription of the pheromone genes and elicits formation of conjugation hyphae. Cyclic AMP and mitogen-activated protein kinase (MAPK) signaling are involved in this process. The MAPK cascade is presumed to be composed of Ubc4 (MAPK kinase kinase), Fuz7 (MAPK kinase), and Ubc3/Kpp2 (MAPK). We isolated the kpp4 gene and found it to be allelic to ubc4. Epistasis analyses with constitutively active alleles of kpp4 and fuz7 substantiate that Kpp4, Fuz7, and Kpp2/Ubc3 are components of the same module. Moreover, we demonstrate that Fuz7 activates Kpp2 and shows interactions in vitro. Signaling via this cascade regulates expression of pheromone-responsive genes, presumably through acting on the transcription factor Prf1. Interestingly, the same cascade is needed for conjugation tube formation, and this process does not involve Prf1. In addition, fuz7 as well as kpp4 deletion strains are nonpathogenic, while kpp2 deletion mutants are only attenuated in pathogenesis. Here we show that strains expressing the unphosphorylatable allele kpp2T182A/Y184F are severely affected in tumor induction and display defects in early infection-related differentiation.

scholarly journals ERK2 phosphorylates the epigenetic regulator CXXC-finger protein 1 (CFP1)

2019 ◽  
Author(s):  
Aroon S. Karra ◽  
Aileen M. Klein ◽  
Svetlana Earnest ◽  
Steve Stippec ◽  
Chonlarat Wichaidit ◽  
...  
Keyword(s):  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Early Gene ◽  
Highly Active ◽  
Finger Protein ◽  
Extracellular Signal ◽  
Epigenetic Regulator ◽  
Mitogen Activated Protein ◽  
Cxxc Finger Protein 1

AbstractBackgroundThe Ras-Raf-MEK-ERK signaling pathway is essential for proper development and homeostatic regulation in eukaryotic cells and underlies progression of several types of cancer. Many pathway functions are performed by extracellular signal-regulated kinase (ERK)1 and 2 (ERK1/2), serine/threonine protein kinases of the mitogen-activated protein kinase (MAPK) family that interact with a large number of substrates and are highly active in the nucleus.ResultsWe identified the epigenetic regulator CXXC-finger protein 1 (CFP1) as a protein that interacts with ERK2 on chromatin. CFP1 is involved in multiple aspects of chromatin regulation, including histone methylation and DNA methylation. Here, we demonstrate the overlapping roles for ERK1/2 and CFP1 in regulation of immediate early gene (IEG) induction. Our work suggests multiple modes of co-regulation and demonstrates that CFP1 is required for an optimal signal-dependent response. We also show that CFP1 is an ERK2 substrate in vitro and identify several phosphorylation sites. Furthermore, we provide evidence that Su(var)3-9, Enhancer-of-zeste and Trithorax (Set)1b, a CFP1-interacting histone methylase, is phosphorylated by ERK2 and is regulated by CFP1.ConclusionOur work highlights ERK1/2 interactions with chromatin regulators that contribute to MAPK signaling diversity in the nucleus.

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