# Novel ARNT-mediated Regulatory Paradigm of AHR Signaling

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $124,999

## Abstract

SUMMARY/ABSTRACT FOR ADMINISTRATIVE SUPPLEMENT: COUNTERACT PROGRAM
 This administrative supplement application is an expansion of aim 3 of my parent R01 grant (ES025809)
where we proposed experiments to examine AHR signaling regulation in macrophages and dendritic cells after
treatment of our myeloid-specific Arnt-a (ARNT isoform 1) transgenic mouse model with AHR-activating
toxicants. Recently, inhaled acrolein, a highly reactive a,b-unsaturated aldehyde and potent respiratory irritant,
was shown to activate AHR in the lungs of exposed mice resulting in disruption of immune cell homeostasis.
Thus, the focus of this supplemental project is to investigate effects of inhaled acrolein on AHR/ARNT signaling
in alveolar macrophages and epithelial cells of Arnt-a transgenic mice versus non-carrier littermate controls. We
predict that myeloid cells are central players in acrolein toxicity, and the experiments outlined in this application
will provide clues to the mechanisms involved. Moreover, acrolein exposure experiments should significantly
further our understanding of ARNT isoform-specific regulation of AHR as it pertains to maintaining immune
homeostasis. To investigate our hypothesis, we propose to 1) Determine the role of AHR/ARNT signaling in
response to acrolein exposure in lung macrophage and epithelial cell lines, in vitro, and 2) Determine the in vivo
characteristics and magnitude of ARNT isoform 1-associated lung toxicity induced by inhaled acrolein in Arnt-a-
transgenic mice.

## Key facts

- **NIH application ID:** 10157334
- **Project number:** 3R01ES025809-05S1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Casey W Wright
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $124,999
- **Award type:** 3
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157334

## Citation

> US National Institutes of Health, RePORTER application 10157334, Novel ARNT-mediated Regulatory Paradigm of AHR Signaling (3R01ES025809-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10157334. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*