Downregulation of TLR4 by miR-181a Provides Negative Feedback Regulation to Lipopolysaccharide-Induced Inflammation
Related Experiment Video
Updated: Feb 13, 2026
Purification and Visualization of Lipopolysaccharide from Gram-negative Bacteria by Hot Aqueous-phenol Extraction
Published on: May 28, 2012
Kangfeng Jiang1, Shuai Guo1, Tao Zhang1
1Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Abstract:
Acute lung injury (ALI) is a progressive clinical disease with a high mortality rate, and characterized by an excessive uncontrolled inflammatory response. MicroRNAs (miRNAs) play a critical role in various human inflammatory diseases, and have been recognized as important regulators of inflammation. However, the regulatory mechanisms mediated by miRNAs involved in Lipopolysaccharide (LPS)-induced inflammation in ALI remain hazy. In this study, we found that miR-181a expression in the lung tissues of ALI mice and LPS-stimulated RAW 264.7 macrophages is dramatically reduced. We also show that over-expression of miR-181a significantly decreased the production of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, whereas inhibition of miR-181a reversed this decrease. Moreover, miR-181a inhibits NF-κB activation and accumulation of reactive oxygen species (ROS) by targeting TLR4 expression. We further verify that miR-181a suppresses TLR4 expression by binding directly to the 3'-UTR of TLR4. Therefore, we provide the first evidence for the negative regulation of miR-181a in LPS-induced inflammation via the suppression of ROS generation and TLR4-NF-κB pathway.
Insights
MicroRNA-181a (miR-181a) is reduced in acute lung injury (ALI). Restoring miR-181a suppresses inflammation by targeting TLR4, inhibiting the NF-κB pathway and reducing reactive oxygen species (ROS).
Area of Science:
- Molecular Biology
- Immunology
- Respiratory Medicine
Background:
- Acute lung injury (ALI) involves uncontrolled inflammation and high mortality.
- MicroRNAs (miRNAs) are key regulators of inflammatory diseases.
- The role of miRNAs in lipopolysaccharide (LPS)-induced ALI inflammation is unclear.
Purpose of the Study:
- Investigate the role of miR-181a in LPS-induced ALI.
- Determine the regulatory mechanism of miR-181a in inflammation.
Main Methods:
- Assessed miR-181a expression in ALI mouse lung tissue and LPS-stimulated macrophages.
- Overexpressed and inhibited miR-181a to evaluate its effects on inflammatory cytokines.
- Investigated the targeting of Toll-like receptor 4 (TLR4) by miR-181a.
- Analyzed the impact on NF-κB activation and reactive oxygen species (ROS) generation.
Main Results:
- miR-181a expression was significantly reduced in ALI models.
- Overexpression of miR-181a decreased inflammatory cytokines (IL-1β, IL-6, TNF-α).
- miR-181a directly targets TLR4, inhibiting NF-κB activation and ROS production.
Conclusions:
- miR-181a negatively regulates LPS-induced inflammation in ALI.
- The mechanism involves suppressing the TLR4-NF-κB pathway and ROS generation.
- miR-181a represents a potential therapeutic target for ALI.
Related Concept Videos
01:23Negative Regulator Molecules
01:18Positive and Negative Feedback Loops
01:27Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:38Inflammation
00:46Feedback Inhibition
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...