ArticlePloS one2015
AS-703026 Inhibits LPS-Induced TNFα Production through MEK/ERK Dependent and Independent Mechanisms.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- MEK Inhibitors and Toll-like Receptor Signaling: Implications for Infection and Inflammation.International journal of molecular sciences · 2026Review
- Distinct longevity mechanisms across and within species and their association with aging.Cell · 2023Article
- The potential role of Hippo pathway regulates cellular metabolism via signaling crosstalk in disease-induced macrophage polarization.Frontiers in immunology · 2023Review
- β-Hydroxyisovalerylshikonin regulates macrophage polarizationPharmaceutical biology · 2022Article
- MAP2K2 Delays Recovery in Murine Models of Acute Lung Injury and Associates with Acute Respiratory Distress Syndrome Outcome.American journal of respiratory cell and molecular biology · 2022Article
- Fragment-Based Discovery of Novel Allosteric MEK1 Binders.ACS medicinal chemistry letters · 2021Article
- Non-cytotoxic doses of shikonin inhibit lipopolysaccharide-induced TNF-α expression via activation of the AMP-activated protein kinase signaling pathway.Experimental and therapeutic medicine · 2020Article
- Article
- Rab5a Promotes Cytolethal Distending Toxin B-Induced Cytotoxicity and Inflammation.Infection and immunity · 2020Article
- Long non-coding RNA Rpph1 promotes inflammation and proliferation of mesangial cells in diabetic nephropathy via an interaction with Gal-3.Cell death & disease · 2019Article
- Dual Role For A MEK Inhibitor As A Modulator Of Inflammation And Host Defense Mechanisms With Potential Therapeutic Application In COPD.International journal of chronic obstructive pulmonary disease · 2019Article
- Article
- Tumor-specific hepatic stellate cells (tHSCs) induces DIgR2 expression in dendritic cells to inhibit T cells.Oncotarget · 2017Article
- DlgR2 knockdown boosts dendritic cell activity and inhibits hepatocellular carcinoma tumorOncotarget · 2017Article
- MEK1/2 Inhibition Promotes Macrophage Reparative Properties.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- miR-135b-5p inhibits LPS-induced TNFα production via silencing AMPK phosphatase Ppm1e.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by intense lung infiltrations of immune cells (macrophages and monocytes). Lipopolysaccharide (LPS) activates macrophages/monocytes, leading to production of tumor necrosis factor α (TNFα) and other cytokines, which cause subsequent lung damages. In the current study, our results demonstrated that AS-703026, a novel MEK/ERK inhibitor, suppressed LPS-induced TNFα mRNA expression and protein secretion in RAW 264.7 murine macrophages, and in murine bone marrow-derived macrophages (BMDMs). Meanwhile, TNFα production in LPS-stimulated COPD patents' peripheral blood mononuclear cells (PBMCs) was also repressed by AS-703026. At the molecular level, we showed that AS-703026 blocked LPS-induced MEK/ERK activation in above macrophages/monocytes. However, restoring ERK activation in AS-703026-treated RAW 264.7 cells by introducing a constitutive-actively (CA)-ERK1 only partially reinstated LPS-mediated TNFα production. Meanwhile, AS-703026 could still inhibit TNFα response in ERK1/2-depleted (by shRNA) RAW 264.7 cells. Significantly, we found that AS-703026 inhibited LPS-induced nuclear factor κB (NFκB) activation in above macrophages and COPD patients' PBMCs. In vivo, oral administration of AS-703026 inhibited LPS-induced TNFα production and endotoxin shock in BALB/c mice. Together, we show that AS-703026 in vitro inhibits LPS-induced TNFα production in macrophages/monocytes, and in vivo protects mice from LPS-induced endotoxin shock. Thus, it could be further studied as a useful anti-inflammatory therapy for COPD patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.