# Regulation of airway epithelial cell-mediated inflammation by CRAC channels

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $464,366

## Abstract

Abstract
Ca2+ is a ubiquitous signaling messenger mediating many essential functions such as
excitability, exocytosis and transcription. In the airway epithelial cells (AECs) lining the
conducting airways of the lung, Ca2+ signals are implicated in numerous cellular functions
through effects on enzymatic cascades and transcriptional factors. Ca2+ homeostasis is also
closely integrated with other signaling systems including that of reactive oxygen species (ROS),
which has many cellular functions of its own and is implicated in allergic lung diseases and
injury. We have recently shown that store-operated Ca2+ release-activated Ca2+ (CRAC)
channels serve as the main pathway for Ca2+ entry in bronchial epithelial cells and their
activation leads to increases in levels of numerous proinflammatory cytokines. However, the
broader significance of CRAC channels in AECs for mediating airway inflammation and potential
crosstalk with ROS and other signaling pathways mediating inflammation remains unknown. We
hypothesize that CRAC channels are a major mechanism for controlling the generation of
inflammatory mediators from AECs in response to stimulation of cell surface G-protein coupled
receptors such as protease-activated and ATP receptors, and are an essential mediator of
pulmonary inflammation in diseases such as asthma. We will address this hypothesis through
three specific goals: 1) examine the physiological contributions of CRAC channels for allergen-
mediated release of ATP and determine how this release stimulates inflammatory cytokines
from AECs, 2) investigate the functional interactions between CRAC channels and
mitochondrial ROS signaling and assess the impact of this crosstalk for inflammatory cytokine
generation, and 3) evaluate the contribution of CRAC channels for mediating airway
inflammation in vivo in a mouse model of house dust mite-induced asthma. Together, these
studies will advance our understanding of how CRAC channels regulate cellular Ca2+-dependent
signaling pathways to modulate allergen-stimulated inflammatory mediators in the airways, and
advance the quest for developing novel treatments for allergic airway diseases.

## Key facts

- **NIH application ID:** 10433909
- **Project number:** 5R01HL149385-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Murali Prakriya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $464,366
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10433909

## Citation

> US National Institutes of Health, RePORTER application 10433909, Regulation of airway epithelial cell-mediated inflammation by CRAC channels (5R01HL149385-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10433909. Licensed CC0.

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