Related Experiment Video

Updated: Oct 2, 2025

In Vivo Imaging of Reactive Oxygen Species in a Murine Wound Model
06:40

In Vivo Imaging of Reactive Oxygen Species in a Murine Wound Model

Published on: November 17, 2018

11.2K

Aberrant HO-1/NQO1-Reactive Oxygen Species-ERK Signaling Pathway Contributes to Aggravation of TPA-Induced Irritant

Junkai Huang1,2, Xiaoyue Feng1,2, Jie Zeng1,2

  • 1Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin, China.

Journal of Immunology (Baltimore, Md. : 1950)
|February 24, 2022
PubMed

Insights

NF-Erythroid 2-related factor 2 (Nrf2) deficiency exacerbates irritant contact dermatitis by increasing inflammation and oxidative stress. The Nrf2/ROS/ERK pathway is crucial in regulating this response.

Area of Science:

  • Immunology
  • Toxicology
  • Molecular Biology

Background:

  • NF-Erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular defense against oxidative stress and toxicants.
  • Nrf2 plays a role in inhibiting contact dermatitis via redox-dependent and -independent mechanisms.
  • The precise mechanisms by which Nrf2 influences irritant contact dermatitis (ICD) remain incompletely understood.

Purpose of the Study:

  • To investigate the role of Nrf2 in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute irritant contact dermatitis (ICD).
  • To elucidate the signaling pathways involved in Nrf2-mediated regulation of TPA-induced ICD.

Main Methods:

  • Utilized Nrf2 knockout mice and mouse embryonic fibroblasts (MEFs) to study TPA-induced acute ICD.
  • Assessed ear thickness, redness, swelling, and neutrophil infiltration.
  • Measured inflammatory cytokine expression and antioxidant gene expression (HO-1, NQO1).
  • Investigated ERK phosphorylation, reactive oxygen species (ROS) accumulation, and the effects of ERK inhibition and ROS scavenging.

Main Results:

  • Nrf2 knockout mice exhibited significantly increased ear thickness, redness, swelling, and neutrophil infiltration compared to controls.
  • Inflammatory cytokine expression (IL-1α, IL-1β, IL-6) was elevated, while antioxidant gene expression (HO-1, NQO1) was decreased in Nrf2 knockout mice.
  • ERK phosphorylation was elevated in Nrf2 knockout MEFs.
  • Inhibition of ERK and ROS scavenging both alleviated TPA-induced inflammation and ROS accumulation in MEFs.

Conclusions:

  • Nrf2 plays a critical protective role in mitigating TPA-induced acute irritant contact dermatitis.
  • The Nrf2/ROS/ERK signaling pathway is a key regulator of TPA-induced acute ICD.
  • Targeting the Nrf2/ROS/ERK pathway may offer therapeutic strategies for managing irritant contact dermatitis.

More Related Videos

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing09:02

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing

Published on: June 9, 2017

23.5K
Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA04:12

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA

Published on: December 19, 2019

14.7K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.4K