# Environmental Pollutants Potentiate Allergic Inflammation via Functional Axis of Aryl hydrocarbon Receptor, ROS, and CaMKII in Asthma

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $577,409

## Abstract

ABSTRACT
Asthma has become increasingly common in the past decade. Co-exposure to environmental pollutants and
allergens can exacerbate allergic sensitization and induce key characteristics of severe asthma. Cockroaches
are a potent source of allergen that can induce sensitization and drive allergic respiratory symptoms.
Interestingly, exposure to polycyclic aromatic hydrocarbons (PAHs), which are diesel exhaust particulates
(DEPs)-derived toxins, can increase the likelihood of developing cockroach allergy and asthma. However, the
underlying molecular mechanisms are currently not well-established. Our long-term goals are to elucidate the
fundamental mechanisms by which environmental pollutants enhance cockroach-induced allergic inflammation
and identify novel therapeutic targets for allergic asthma. Our more specific aims are to address the hypothesis
that alterations in recruitment and function of mast cells play a heretofore underappreciated role in the positive
interactions between environmental pollutants and airway allergic inflammation. Aryl hydrocarbon receptor (AhR)
is a receptor for common environmental contaminants. AHR has been shown to be a key receptor in driving
environmental pollutant-enhanced allergic lung inflammation. We have recently made significant contributions to
unraveling the function of AhR signaling in mast cell activation and allergic inflammation. We were the first to
characterize the essential role of oxidative activation of calmodulin-dependent protein kinase II (ox-CaMKII) in
AhR mediated mast cell activation and ROS production. Furthermore, recent discoveries suggest that
mitochondrial-targeted inhibition of CaMKII in airway epithelium suppresses mitochondrial ROS generation and
protects against allergic asthma. Thus, these findings raise the possibility that CaMKII is a central player sensing
“upstream” ROS and controlling “downstream” mitochondrial ROS generation, mast cell activation and
characteristic features of allergic asthma. These exciting new data set the stage to test our central hypothesis:
AhR mediates environmental pollutant-potentiated allergen-induced mitochondrial ROS generation and oxidative
activation of CaMKII, which are essential for mast cell activation and development of allergic asthma. Three
independent yet related specific aims are proposed. Aim 1 proposes studies to determine whether epithelial AhR
plays a role in mediating environmental pollutant-enhanced allergen-induced epithelial mitochondrial ROS
generation, cytokine release, and mast cell recruitment in asthma. Aim 2 proposes experiments to define whether
AhR on mast cells mediates environmental pollutant-enhanced allergen-induced mitochondrial CaMKII that
contributes to ROS generation and oxidative activation of CaMKII. Aim 3 proposes studies to elucidate the role
of oxidative activation of CaMKII in mast cell activation and allergic asthma and to explore the possible
mechanisms. The proposed research is significant as it will pro...

## Key facts

- **NIH application ID:** 9960432
- **Project number:** 5R01AI141642-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Peisong Gao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $577,409
- **Award type:** 5
- **Project period:** 2019-06-19 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960432

## Citation

> US National Institutes of Health, RePORTER application 9960432, Environmental Pollutants Potentiate Allergic Inflammation via Functional Axis of Aryl hydrocarbon Receptor, ROS, and CaMKII in Asthma (5R01AI141642-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9960432. Licensed CC0.

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