Related Experiment Video

Updated: Jan 20, 2026

Studying Effects of Cigarette Smoke on Pseudomonas Infection in Lung Epithelial Cells
09:15

Studying Effects of Cigarette Smoke on Pseudomonas Infection in Lung Epithelial Cells

Published on: May 11, 2020

6.4K

Blockade of EGFR Activation Promotes TNF-Induced Lung Epithelial Cell Apoptosis and Pulmonary Injury

Toshimitsu Yamaoka1,2, Satoru Arata3, Mayumi Homma4

  • 1Advanced Cancer Translational Research Institute, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. yamaoka.t@med.showa-u.ac.jp.

International Journal of Molecular Sciences
|August 21, 2019
PubMed

Insights

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) can cause lung inflammation. This study reveals EGFR inhibition increases lung cell death, suggesting EGFR protects against lung injury during cancer treatment.

Area of Science:

  • Pulmonary Medicine
  • Oncology
  • Cell Biology

Background:

  • Pneumonitis is a major cause of death in non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).
  • The precise mechanisms and risk factors for TKI-induced pneumonitis remain unclear.
  • Tumor necrosis factor (TNF) is known to activate EGFR in lung cells.

Purpose of the Study:

  • To investigate the role of EGFR tyrosine kinase activity in regulating TNF-mediated bronchial epithelial cell survival.
  • To determine if inhibiting EGFR activity exacerbates TNF-induced lung epithelial cell apoptosis.

Main Methods:

  • Utilized surfactant protein C (SPC)-TNF transgenic mice overexpressing TNF in the lungs.
  • Administered gefitinib, an EGFR-TKI, to the transgenic mice.
  • Examined lung epithelial cells (BEAS-2B) stimulated with TNF in vitro.

Main Results:

  • Gefitinib treatment in SPC-TNF tg mice led to increased lung epithelial cell apoptosis and lymphocytic inflammation.
  • EGFR inhibition by gefitinib upregulated IL-17A and activated p38MAPK in the mouse model.
  • In lung epithelial cells, TNF induced EGFR transactivation via TNF-α-converting enzyme, dependent on heparin binding (HB)-EGF and transforming growth factor (TGF)-α.

Conclusions:

  • EGFR tyrosine kinase activity plays a protective role against TNF-induced lung injury.
  • EGFR inhibition may increase susceptibility to lung epithelial cell apoptosis.
  • Findings provide insights into EGFR's role in maintaining lung epithelial homeostasis and NSCLC treatment strategies.
Keywords:
EGFRTNFapoptosislung injurytransactivation

More Related Videos

Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury08:27

Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury

Published on: May 21, 2018

11.4K
Pseudomonas aeruginosa Induced Lung Injury Model07:24

Pseudomonas aeruginosa Induced Lung Injury Model

Published on: October 29, 2014

19.0K

Related Concept Videos

Neuromuscular Junction And Blockade01:29

Neuromuscular Junction And Blockade

The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
4.8K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
14.2K
Lung Capacity01:47

Lung Capacity

The air in the lungs is measured in volumes and capacities. Lung volume measures reflect the amount of air taken in, released, or left over after a lung function, like a single inhalation. Lung capacity measures are sums of two or more lung volume measures.
56.1K
The Eukaryotic Promoter Region02:40

The Eukaryotic Promoter Region

The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
18.7K
The Eukaryotic Promoter Region02:40

The Eukaryotic Promoter Region

3.8K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
509