# Epithelial regulation of ECM and leukocyte adhesion in viral-triggered asthma

> **NIH NIH U19** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2020 · $329,227

## Abstract

Project Summary
The overarching hypothesis of this Program is that the airway epithelium serves as a central coordinator of the
responses to respiratory virus infection, and that sensitization to aeroallergens and intrinsic differences in
airway epithelial cells (AECs) between asthmatic and healthy individuals is the critical link between exposure
and the development of dysfunctional airway responses in asthma. In Project 1, we will investigate the role of
AEC-derived TGFβ in regulating airway ECM composition, including regulation of VCAN and HA accumulation
and their degradation products in the airway ECM leading to increased adhesion and activation of inflammatory
leukocytes. Based upon observations by our group and others, and additional preliminary data presented in
Project 1, we hypothesize that viral infection with RSV or HRV, and allergen exposure with the common
aeroallergens cockroach antigen (CRA) or house dust mite (HDM), of AECs from asthmatic as compared to
healthy children induce human lung fibroblasts (HLFs) to produce an airway ECM enriched with VCAN, HA and
their degradation products, leading to increased adhesion and activation of inflammatory leukocytes. We will
test this global hypothesis and investigate mechanisms responsible for airway matrix dysregulation in asthma,
and the resulting increased adhesion and activation of leukocytes. Using human asthmatic AEC and AEC/HLF
co-cultures we will determine the effects of viral infection and aeroallergen exposure with CRA and HDM, on
asthmatic AEC regulation of HLF ECM production and composition. Furthermore, we will determine the effects
of asthmatic AEC infection by respiratory viruses and exposure to CRA or HDM antigen on leukocyte adhesion
to and activation by ECM produced by HLF. Finally, using a murine model of viral-triggered asthma we will
determine the role of epithelium in regulating cellular responses during viral infection and exacerbation.

## Key facts

- **NIH application ID:** 9959315
- **Project number:** 5U19AI125378-05
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** Steven F Ziegler
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $329,227
- **Award type:** 5
- **Project period:** 2016-07-15 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959315

## Citation

> US National Institutes of Health, RePORTER application 9959315, Epithelial regulation of ECM and leukocyte adhesion in viral-triggered asthma (5U19AI125378-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9959315. Licensed CC0.

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