scholarly journals IL1β Promotes TMPRSS2 Expression and SARS-CoV-2 Cell Entry Through the p38 MAPK-GATA2 Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chiara Cioccarelli ◽  
Ricardo Sánchez-Rodríguez ◽  
Roberta Angioni ◽  
Francisca C. Venegas ◽  
Nicole Bertoldi ◽  
...  
Keyword(s):  
Disease Progression ◽  
Molecular Mechanism ◽  
P38 Mapk ◽  
Inflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Research Effort ◽  
Cell Entry ◽  
Cytokine Milieu ◽  
Inflammatory Milieu

After the outburst of the SARS-CoV-2 pandemic, a worldwide research effort has led to the uncovering of many aspects of the COVID-19, among which we can count the outstanding role played by inflammatory cytokine milieu in the disease progression. Despite that, molecular mechanisms that regulate SARS-CoV-2 pathogenesis are still almost unidentified. In this study, we investigated whether the pro-inflammatory milieu of the host affects the susceptibility of SARS-CoV-2 infection by modulating ACE2 and TMPRSS2 expression. Our results indicated that the host inflammatory milieu favors SARS-CoV-2 infection by directly increasing TMPRSS2 expression. We unveiled the molecular mechanism that regulates this process and that can be therapeutically advantageously targeted.

p38 MAPK Signaling in Oral-related Diseases

2007 ◽  
Vol 86 (9) ◽  
pp. 812-825 ◽  
Author(s):  
C.S. Patil ◽  
K.L. Kirkwood
Keyword(s):  
P38 Mapk ◽  
Stress Responses ◽  
Intracellular Signaling ◽  
Inflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Periodontal Diseases ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Dental Diseases

Multiple dental diseases are characterized by chronic inflammation, due to the production of cytokines, chemokines, and prostanoids by immune and non-immune cells. Membrane-bound receptors provide a link between the extracellular environment and the initiation of intracellular signaling events that activate common signaling components, including p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor (NF)-κB. Although ERK pathways regulate cell survival and are responsive to extracellular mitogens, p38 MAPK, JNK, and NF-κB are involved in environmental stress responses, including inflammatory stimuli. Over the past decade, significant advances have been made relative to our understanding of the fundamental intracellular signaling mechanisms that govern inflammatory cytokine expression. The p38 MAPK pathway has been shown to play a pivotal role in inflammatory cytokine and chemokine gene regulation at both the transcriptional and the post-transcriptional levels. In this review, we present evidence for the significance of p38 MAPK signaling in diverse dental diseases, including chronic pain, desquamative disorders, and periodontal diseases. Additional information is presented on the molecular mechanisms whereby p38 signaling controls post-transcriptional gene expression in inflammatory states.

scholarly journals The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1828
Author(s):  
Jared Kirui ◽  
Yara Abidine ◽  
Annasara Lenman ◽  
Koushikul Islam ◽  
Yong-Dae Gwon ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Molecular Mechanisms ◽  
Rna Virus ◽  
Ectopic Expression ◽  
Point Mutations ◽  
Cell Entry ◽  
Target Cells ◽  
Human Hepatoma Cells ◽  
Chikv Infection ◽  
Phosphatidylserine Receptor

Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.

Cellular and molecular mechanisms of statins: an update on pleiotropic effects

2015 ◽  
Vol 129 (2) ◽  
pp. 93-105 ◽  
Author(s):  
Mamoru Satoh ◽  
Yuji Takahashi ◽  
Tsuyoshi Tabuchi ◽  
Yoshitaka Minami ◽  
Makiko Tamada ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Chronic Inflammation ◽  
Molecular Mechanism ◽  
Coronary Atherosclerosis ◽  
Molecular Mechanisms ◽  
Cell Injury ◽  
Plaque Instability ◽  
Beneficial Effects ◽  
Reductase Inhibitors ◽  
Artery Disease

Coronary artery disease (CAD) is the leading cause of death worldwide. The efficacy and safety of statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) in primary and secondary prevention of CAD are confirmed in several large studies. It is well known that statins have some pleiotropic, anti-atherosclerotic effects. We review the molecular mechanisms underlying the beneficial effects of statins revealed in recently published studies. Endothelial cell injury is regarded as the classic stimulus for the development of atherosclerotic lesions. In addition, the inflammatory process plays an important role in the aetiology of atherosclerosis. In particular, chronic inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. Our previous reports and others have demonstrated beneficial effects of statins on endothelial dysfunction and chronic inflammation in CAD. A better understanding of the molecular mechanism underlying the effectiveness of statins against atherosclerosis may provide a novel therapeutic agent for the treatment of coronary atherosclerosis. The present review summarizes the cellular and molecular mechanism of statins against coronary atherosclerosis.

scholarly journals Hypoxia-Induced Epithelial-Mesenchymal Transition Is Involved in Bleomycin-Induced Lung Fibrosis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Liang Guo ◽  
Jun-mei Xu ◽  
Lei Liu ◽  
Su-mei Liu ◽  
Rong Zhu
Keyword(s):  
P38 Mapk ◽  
Lung Fibrosis ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Severe Disease ◽  
Progressive Increase ◽  
Lung Epithelial Cells ◽  
Cellular Mechanisms ◽  
Mesenchymal Transition ◽  
Protein Levels

Pulmonary fibrosis is a severe disease that contributes to the morbidity and mortality of a number of lung diseases. However, the molecular and cellular mechanisms leading to lung fibrosis are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in bleomycin-induced lung fibrosis. The bleomycin-induced fibrosis animal model was established by intratracheal injection of a single dose of bleomycin. Protein expression was measured by Western blot, immunohistochemistry, and immunofluorescence. Typical lesions of lung fibrosis were observed 1 week after bleomycin injection. A progressive increase in MMP-2, S100A4,α-SMA, HIF-1α, ZEB1, CD44, phospho-p44/42 (p-p44/42), and phospho-p38 MAPK (p-p38) protein levels as well as activation of EMT was observed in the lung tissues of bleomycin mice. Hypoxia increased HIF-1αand ZEB1 expression and activated EMT in H358 cells. Also, continuous incubation of cells under mild hypoxic conditions increased CD44, p-p44/42, and p-p38 protein levels in H358 cells, which correlated with the increase in S100A4 expression. In conclusion, bleomycin induces progressive lung fibrosis, which may be associated with activation of EMT. The fibrosis-induced hypoxia may further activate EMT in distal alveoli through a hypoxia-HIF-1α-ZEB1 pathway and promote the differentiation of lung epithelial cells into fibroblasts through phosphorylation of p38 MAPK and Erk1/2 proteins.

scholarly journals Baicalin attenuates lipopolysaccharide-induced pro-inflammatory cytokine expression in murine macrophage cell line RAW264.7 through miR-124-STAT3 axis

2018 ◽  
Vol 16 ◽  
pp. 205873921879846 ◽  
Author(s):  
Bin Tang ◽  
Xixi Wang ◽  
Yuqing Zhu ◽  
Xuhui Li ◽  
Shukun Yao
Keyword(s):  
Cell Line ◽  
Molecular Mechanism ◽  
Inflammatory Cytokine ◽  
Inflammatory Factors ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Necrosis Factor Alpha ◽  
Scutellaria Baicalensis Georgi ◽  
Stat3 Signaling Pathway ◽  
Wide Range

Baicalin, a flavonoid isolated from Scutellaria baicalensis Georgi, has shown a wide range of anti-inflammatory, antioxidative, antiviral, and antitumor properties. However, the molecular mechanism of how baicalin exerts its effects, especially on inflammation regulation, has not been fully investigated. In this article, we report the effects of baicalin on the mouse macrophage cell line RAW264.7. Our results demonstrate that baicalin inhibits the production of inflammatory factors interleukin-6 and tumor necrosis factor-alpha upon lipopolysaccharide stimulation of macrophages. We observed that baicalin inhibits STAT3 activation through retarding its expression and phosphorylation. Interestingly, baicalin treatment promotes the elevation of miR-124 in lipopolysaccharide-treated macrophages. Overexpression of the miR-124 mimic in RAW264.7 reduced STAT3 expression and phosphorylation. Furthermore, inhibition of miR-124 attenuated the dysregulation of STAT3 and reduction of inflammatory factors upon baicalin treatment. Our results revealed the molecular mechanism that baicalin attenuates pro-inflammatory cytokine production through miR-124-STAT3 signaling pathway, suggesting that miR-124 is an important modulator in regulating anti-inflammation by baicalin in macrophages.

scholarly journals Fucosterol Protects against Concanavalin A-Induced Acute Liver Injury: Focus on P38 MAPK/NF-κB Pathway Activity

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Wenhui Mo ◽  
Chengfen Wang ◽  
Jingjing Li ◽  
Kan Chen ◽  
Yujing Xia ◽  
...  
Keyword(s):  
Liver Injury ◽  
P38 Mapk ◽  
Concanavalin A ◽  
Molecular Mechanisms ◽  
Therapeutic Agent ◽  
Acute Liver Injury ◽  
Biological Activities ◽  
Hepatic Necrosis ◽  
Protective Effects ◽  
Eisenia Bicyclis

Objective. Fucosterol is derived from the brown alga Eisenia bicyclis and has various biological activities, including antioxidant, anticancer, and antidiabetic properties. The aim of this study was to investigate the protective effects of fucosterol pretreatment on Concanavalin A- (ConA-) induced acute liver injury in mice, and to understand its molecular mechanisms. Materials and Methods. Acute liver injury was induced in BALB/c mice by ConA (25 mg/kg), and fucosterol (dissolved in 2% DMSO) was orally administered daily at doses of 25, 50, and 100 mg/kg. The levels of hepatic necrosis, apoptosis, and autophagy associated with inflammatory cytokines were measured at 2, 8, and 24 h. Results. Fucosterol attenuated serum liver enzyme levels and hepatic necrosis and apoptosis induced by TNF-α, IL-6, and IL-1β. Fucosterol also inhibited apoptosis and autophagy by upregulating Bcl-2, which decreased levels of functional Bax and Beclin-1. Furthermore, reduced P38 MAPK and NF-κB signaling were accompanied by PPARγ activation. Conclusion. This study showed that fucosterol could alleviate acute liver injury induced by ConA by inhibiting P38 MAPK/PPARγ/NF-κB signaling. These findings highlight that fucosterol is a promising potential therapeutic agent for acute liver injury.

scholarly journals Size uniformity of animal cells is actively maintained by a p38 MAPK-dependent regulation of G1-length

2017 ◽  
Author(s):  
Shixuan Liu ◽  
Miriam B. Ginzberg ◽  
Nish Patel ◽  
Marc Hild ◽  
Bosco Leung ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
P38 Mapk ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Small Cells ◽  
Animal Cells ◽  
Cycle Progression ◽  
Size Uniformity

AbstractAnimal cells within a tissue typically display a striking regularity in their size. To date, the molecular mechanisms that control this uniformity are still unknown. We have previously shown that size uniformity in animal cells is promoted, in part, by size-dependent regulation of G1 length. To identify the molecular mechanisms underlying this process, we performed a large-scale small molecule screen and found that the p38 MAPK pathway is involved in coordinating cell size and cell cycle progression. Small cells display higher p38 activity and spend more time in G1 than larger cells. Inhibition of p38 MAPK leads to loss of the compensatory G1 length extension in small cells, resulting in faster proliferation, smaller cell size and increased size heterogeneity. We propose a model wherein the p38 pathway responds to changes in cell size and regulates G1 exit accordingly, to increase cell size uniformity.One-sentence summaryThe p38 MAP kinase pathway coordinates cell growth and cell cycle progression by lengthening G1 in small cells, allowing them more time to grow before their next division.

scholarly journals Polar relaxation by dynein-mediated removal of cortical myosin II

2020 ◽  
Vol 219 (8) ◽  
Author(s):  
Bernardo Chapa-y-Lazo ◽  
Motonari Hamanaka ◽  
Alexander Wray ◽  
Mohan K. Balasubramanian ◽  
Masanori Mishima
Keyword(s):  
Recent Work ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Myosin Ii ◽  
Cell Cortex ◽  
Cleavage Furrow ◽  
Contractile Ring ◽  
C Elegans ◽  
Polar Cell

Nearly six decades ago, Lewis Wolpert proposed the relaxation of the polar cell cortex by the radial arrays of astral microtubules as a mechanism for cleavage furrow induction. While this mechanism has remained controversial, recent work has provided evidence for polar relaxation by astral microtubules, although its molecular mechanisms remain elusive. Here, using C. elegans embryos, we show that polar relaxation is achieved through dynein-mediated removal of myosin II from the polar cortexes. Mutants that position centrosomes closer to the polar cortex accelerated furrow induction, whereas suppression of dynein activity delayed furrowing. We show that dynein-mediated removal of myosin II from the polar cortexes triggers a bidirectional cortical flow toward the cell equator, which induces the assembly of the actomyosin contractile ring. These results provide a molecular mechanism for the aster-dependent polar relaxation, which works in parallel with equatorial stimulation to promote robust cytokinesis.

scholarly journals Beneficial Impact and Molecular Mechanism of Bacillus Coagulans on Piglets Intestine

2018 ◽  
Author(s):  
Tao Wu ◽  
Yang Lv ◽  
Xueni Li ◽  
Lin Zhang ◽  
Yutao Shi ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Bacillus Coagulans ◽  
Basal Diet ◽  
Control Group ◽  
Villus Height ◽  
Intestinal Integrity ◽  
Beneficial Impact ◽  
Related Proteins

This research was to investigate beneficial impact and molecular mechanism of B. coagulans on piglets intestine. Twenty-four 21 days old weaned piglets were allotted to three treatments: control group (basal diet), B6 group (basal diet + 2×106 CFU/g B. coagulans), B7 group (basal diet + 2×107 CFU/g B. coagulans). The results showed that compared with control group, B6 and B7 group significantly decreased diarrhea rate and the concent of CHOL, GGT and DAO in plasma; decreased villus height and increase crypt depth in jejunum and ileum; increased the activities of SOD and CAT and decreased the concent of MDA and H2O2 in intestine. These data suggested that supplementing B. coagulans had beneficial impacts on promoting nutrients metabolism, maintaining intestinal integrity and alleviating oxidative stress and diarrhea. Futher research of molecular mechanisms showed that, these beneficial impacts were regulated by changing expression levels of related proteins (including HSP70, Caspase-3, Bax, Villin and Occludin), and genes (including RPL4, IFN-α, IFN-β, IFN-γ, MX1, MX2, OAS1, IL-1β, IL-4, CXCL-9, CCL-2, AQP3, SGLT-1, LPL, INSR and b0,+AT), and altering community composition of gut microbiota (particularly family Clostridiaceae, Enterobacteriaceae, and Veillonellaceae and genus Prevotella, Turicibacter, and Lactobacillus).

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