scholarly journals Chức năng của miR-146b-5p trong Chondrocyte

2021 ◽  
Vol 16 (1) ◽  
pp. 5-24
Author(s):  
Lê Thi Trúc Linh ◽  
Lê Huyền Ái Thuý
Keyword(s):  
P38 Mapk ◽  
Toll Like Receptor

MicroRNA (miR, miRNA) là một phân tử RNA nhỏ có chiều dài từ 20 đến 25 nucleotide quy định sự biểu hiện của gene bằng cách liên kết đặc hiệu với trình tự 3’UTR trên mRNA đích. Trước đây, chúng tôi nhận thấy miR-146b-5p tuần hoàn tăng đáng kể trong huyết thanh của bệnh nhân Thoái Hoá Khớp (THK) và có thể có tiềm năng rất lớn để chẩn đoán bệnh sớm. Tuy nhiên, chức năng của miRNA này trong THK vẫn chưa được biết và cần được xác định. Vì vậy, nghiên cứu này được thực hiện nhằm xác định chức năng miR-146b-5p trong tế bào chondrocyte. Công cụ tin sinh học được thực hiện để dự đoán các con đường tín hiệu tiềm năng có tương tác với miRNA-146b-5p trong tế bào chondrocyte. Trong đó dữ liệu giải trình tự thế hệ mới cho mRNA có thể được biểu hiện trong tế bào khớp có sẵn trước đó được sử dụng. Dữ liệu cho thấy miR-146b-5p có thể tương tác với một số con đường tín hiệu quan trọng bao gồm Wnt, Notch, Toll like receptor, P38 MAPK, Anti apoptosis, Adhesion, Cadherin, Intergin. Do đó, sự biểu hiện bất thường của microRNA 146-5p có thể dẫn đến đến thoái hoá khớp ít nhất có thể là do rối loạn các đường truyền tín hiệu này.

Cell-free extracts of Propionibacterium acnes stimulate cytokine production through activation of p38 MAPK and Toll-like receptor in SZ95 sebocytes

Life Sciences ◽  
2015 ◽  
Vol 139 ◽  
pp. 123-131 ◽  
Author(s):  
Yu-Chun Huang ◽  
Chao-Hsun Yang ◽  
Ting-Ting Li ◽  
Christos C. Zouboulis ◽  
Han-Chi Hsu
Keyword(s):  
P38 Mapk ◽  
Cytokine Production ◽  
Propionibacterium Acnes ◽  
Toll Like Receptor

scholarly journals ADAM17-Mediated Ectodomain Shedding of Toll-Like Receptor 4 as a Negative Feedback Regulation in Lipopolysaccharide-Activated Aortic Endothelial Cells

2018 ◽  
Vol 45 (5) ◽  
pp. 1851-1862 ◽  
Author(s):  
Won Seok Yang ◽  
Jin Ju Kim ◽  
Mee Jeong Lee ◽  
Eun Kyoung Lee ◽  
Su-Kil Park
Keyword(s):  
Endothelial Cells ◽  
P38 Mapk ◽  
Ectodomain Shedding ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Toll Like Receptor 4 ◽  
Negative Feedback Regulation ◽  
Mapk Activation ◽  
Aortic Endothelial Cells ◽  
Aortic Endothelial

Background/Aims: Lipopolysaccharide (LPS)-activated monocytes/macrophages develop endotoxin tolerance in part by reducing cell surface toll-like receptor 4 (TLR4) through cluster of differentiation 14 (CD14)-dependent endocytosis. In case of endothelial cells, CD14 is expressed in low copy numbers as compared with monocytes/macrophages. Thus, we explored how endothelial cells regulate TLR4 expression after LPS stimulation. Methods: Cultured human aortic endothelial cells (HAECs) were treated with LPS. TLR4 expression was analyzed by Western blot analysis and immunofluorescence staining. A disintegrin and metalloprotease 17 (ADAM17) activity was measured using a fluorescent substrate. Results: TLR4 in cell lysate began to decrease within 30 min of LPS treatment with a maximal reduction at 2 h, and it was accompanied by an increase of N-terminal fragment of TLR4 in culture supernatant, indicating ectodomain shedding of the receptor. LPS activated p38 mitogen-activated protein kinase (p38 MAPK) and ADAM17, while LPS-induced ADAM17 activation was inhibited by SB203580, a p38 MAPK inhibitor. LPS-induced ectodomain shedding of TLR4 was attenuated by siRNA depletion of ADAM17 as well as TAPI-2 (an inhibitor of ADAM family) and SB203580. LPS pretreatment resulted in a blunted response of p38 MAPK activation to further LPS stimulation. In the cells depleted of ADAM17, LPS-induced p38 MAPK activation was prolonged and LPS-induced intercellular adhesion molecule-1 expression was potentiated. Conclusion: HAECs respond to LPS by rapid shedding of the ectodomain of TLR4 and thereby reduce the responsiveness to subsequent LPS exposure. ADAM17, downstream of p38 MAPK, is implicated in the ectodomain cleavage of TLR4.

Lipopolysaccharide inhibits GPR120 expression in macrophages via Toll‐like receptor 4 and p38 MAPK activation

2019 ◽  
Vol 44 (1) ◽  
pp. 89-97 ◽  
Author(s):  
Yan‐Yan Zhao ◽  
Hui Fu ◽  
Xiang‐Yan Liang ◽  
Bi‐Lin Zhang ◽  
Lan‐Lan Wei ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Mapk Activation

Atorvastatin suppresses LPS-induced rapid upregulation of Toll-like receptor 4 and its signaling pathway in endothelial cells

2011 ◽  
Vol 300 (5) ◽  
pp. H1743-H1752 ◽  
Author(s):  
Ying Wang ◽  
Ming Xiang Zhang ◽  
Xiao Meng ◽  
Fu Qiang Liu ◽  
Guang Sheng Yu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Umbilical Vein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Mapk Phosphorylation ◽  
Tlr4 Mrna

In the present study, we tested our hypothesis that atorvastatin exerts its anti-inflammation effect via suppressing LPS-induced rapid upregulation of Toll-like receptor 4 (TLR4) mRNA and its downstream p38, ERK, and NF-κB signaling pathways in human umbilical-vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs). TLR4 mRNA expression and its downstream kinase activities induced by LPS alone or atorvastatin + LPS in endothelial cells were quantified using quantitative real-time PCR and enzyme-linked immunosorbent assay. Preincubation of LPS-stimulated endothelial cells with TLR4 siRNA was conducted to identify the target of the anti-inflammatory effects of atorvastatin. Atorvastatin incubation resulted in the reduction of LPS-induced TLR4 mRNA expression, ERK1/2 and P38 MAPK phosphorylation, and NF-κB binding activity. Pretreatment with MEK/ERK1/2 inhibitor PD98059 attenuated atorvastatin + LPS-induced NF-κB activity but had no effect on P38 MAPK phosphorylation. In contrast, pretreatment with P38 MAPK inhibitor SB203580 resulted in upregulation of atorvastatin + LPS-induced ERK1/2 phosphorylation but had no significant effects on NF-κB activity. On the other hand, blocking NF-κB with SN50 produced no effects on atorvastatin + LPS-induced ERK1/2 and P38 MAPK phosphorylation. Moreover, TLR4 gene silencing produced the same effects as the atorvastatin treatment. In conclusion, atorvastatin downregulated TLR4 mRNA expression by two distinct signaling pathways. First, atorvastatin stabilized Iκ-Bα, which directly inhibited NF-κB activation. Second, atorvastatin inactivated ERK phosphorylation, which indirectly inhibited NF-κB activation. Suppression of p38 MAPK by atorvastatin upregulates ERK but exerts no effect on NF-κB.

scholarly journals A Novel Role of Numb as A Regulator of Pro-inflammatory Cytokine Production in Macrophages in Response to Toll-like Receptor 4

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Patipark Kueanjinda ◽  
Sittiruk Roytrakul ◽  
Tanapat Palaga
Keyword(s):  
Notch Signaling ◽  
P38 Mapk ◽  
Inflammatory Responses ◽  
Notch Signaling Pathway ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Murine Bone Marrow

Abstract Activation of macrophages triggers the release of pro-inflammatory cytokines leading to inflammation. Numb is a negative regulator of Notch signaling, but the role of Numb in macrophages is not fully understood. In this study, the role of Numb as a regulator of inflammatory responses in macrophages was investigated. Murine bone marrow-derived macrophages, in which expression of Numb was silenced, secreted significantly less TNFα, IL-6 and IL-12 and more IL-10 upon activation by lipopolysaccharide (LPS), a ligand for Toll-like receptor 4 (TLR4), despite increased Notch signaling. The Tnfα mRNA levels both in Numb-deficient and wild-type macrophages were not significantly different, unlike those of Il6 and Il12-p40. In Numb-deficient macrophages, the Tnfα mRNAs were degraded at faster rate, compared to those in control macrophages. Activation of p38 MAPK and NF-κΒ p65 were compromised in activated Numb deficient macrophages. Numb was found to interact with the E3 ubiquitin ligase, Itch, which reportedly regulates p38 MAPK. In addition, blocking the Notch signaling pathway in activated, Numb-deficient macrophages did not further reduce TNFα levels, suggesting a Notch-independent role for Numb. A proteomics approach revealed a novel funciton for Numb in regulating complex signaling cascades downstream of TLRs, partially involving Akt/NF-κB p65/p38 MAPK in macrophages.

scholarly journals Inhibition of LPS-Induced Activation of Coagulation by p38 MAPK Inhibitor

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Lutz Koch ◽  
Stefan Hofer ◽  
Markus A. Weigand ◽  
David Frommhold ◽  
Johannes Poeschl ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Sandwich Elisa ◽  
Mitogen Activated Protein Kinase ◽  
Toll Like Receptor ◽  
Inhibitory Effects ◽  
Coagulation Activation ◽  
Mitogen Activated Protein ◽  
P38 Mapk Inhibitor ◽  
Mapk Inhibitor

During Gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of immune system and coagulation. However, the underlying LPS signalling mechanism on coagulation activation remains complex. To determine the role of the intracellular signalling factors p38 mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and c-Jun N-terminal kinase (JNK) in the procoagulant response to LPS, coagulation process of human whole blood exposed to specific inhibitors was measured by thrombelastography. Samples were stimulated with LPS (100 μg/mL) after preincubation with BAY117082 (specific NF-κB inhibitor), SP600125 (specific JNK inhibitor), SB203580 (specific p38 MAPK inhibitor), or vehicle. SB203580 strongly inhibited LPS-induced coagulation activation, whereas BAY117082 and SP600125 showed no significant effect. Activation of p38 MAPK, NF-κB, and JNK and respective inhibitory effects were confirmed by Multi-Target Sandwich ELISA. In conclusion, activation of p38 MAPK is crucial for early LPS-induced activation of coagulation.

scholarly journals Herbal melanin induces interleukin‑1β secretion and production by human THP‑1 monocytes via Toll‑like receptor 2 and p38 MAPK activation

2021 ◽  
Vol 22 (4) ◽  
Author(s):  
Adila El‑Obeid ◽  
Wesam Yahya ◽  
Bader Almuzzaini ◽  
Abeer Tuwaijri ◽  
Maria Najdi ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Interleukin 1Β ◽  
Toll Like Receptor ◽  
Mapk Activation ◽  
Toll Like Receptor 2

scholarly journals Macrophage glucocorticoid receptors regulate Toll-like receptor 4–mediated inflammatory responses by selective inhibition of p38 MAP kinase

Blood ◽  
2007 ◽  
Vol 109 (10) ◽  
pp. 4313-4319 ◽  
Author(s):  
Sandip Bhattacharyya ◽  
Diane E. Brown ◽  
Judson A. Brewer ◽  
Sherri K. Vogt ◽  
Louis J. Muglia
Keyword(s):  
Map Kinase ◽  
P38 Mapk ◽  
Glucocorticoid Receptors ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Specific Inhibitor ◽  
P38 Map Kinase ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Map Kinase Phosphatase

Abstract To explore the role of glucocorticoids in regulation of kinase pathways during innate immune responses, we generated mice with conditional deletion of glucocorticoid receptor (GR) in macrophages (MGRKO). Activation of toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) caused greater mortality and cytokine production in MGRKO mice than in controls. Ex vivo, treatment with dexamethasone (Dex) markedly inhibited LPS-mediated induction of inflammatory genes in control but not GR-deficient macrophages. We show that Dex inhibits p38 MAPK, but not PI3K/Akt, ERK, or JNK, in control macrophages. Associated with p38 inhibition, Dex induced MAP kinase phosphatase-1 (MKP-1) in control, but not MGRKO, macrophages. Consistent with the ex vivo studies, treatment with a p38 MAPK–specific inhibitor resulted in rescue of MGRKO mice from LPS-induced lethality. Taken together, we identify p38 MAPK and its downstream targets as essential for GR-mediated immunosuppression in macrophages.

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