# Mechanisms of Rhinovirus-induced airway hyperresponsiveness: an airway smooth muscle perspective

> **NIH NIH R56** · RUTGERS BIOMEDICAL/HEALTH SCIENCES-RBHS · 2020 · $404,167

## Abstract

Project Summary:
Rhinoviruses (RV) have been impugned in the development of asthma and are the leading cause of acute
asthma exacerbations. RV exposure elicits inflammation of the airways, but how RV modulates human airway
smooth muscle cell (HASM) function to engender airway hyperresponsiveness (AHR) is unclear. HASM is the
pivotal cell modulating bronchomotor tone, shortening in response to contractile agonist stimulation through
increases in intracellular calcium, through activation of Rho kinase, and through modulation of actin dynamics.
We show that RV exposure evokes AHR in human precision cut lung slices (hPCLS), increases [Ca2+]i in HASM,
and increases agonist-induced phosphorylation of myosin light chain in HASM from human airway epithelial cell
(HAEC)/HASM co-cultures stimulated with RV-C15. We also demonstrate that RVC attenuates β2 agonist-
induced bronchodilation in hPCLS and cAMP production in HASM. Additionally, we show that VEGF exposure
of hPCLS induces AHR and attenuates bronchodilation of small airways. Therefore we posit RVC modulates
both contractile and relaxation signaling in HASM to alter responsiveness of the airways. We propose a central
hypothesis that RVC exposure of HAEC induces release of VEGF to: (1) promote AHR via the modulation
of calcium mobilization, and (2) attenuate β2 agonist-induced bronchodilation via modulation of cAMP-
mobilizing pathways. We will utilize HASM cells, air-liquid interface-differentiated HAEC, and hPCLS to
examine the aims of this proposal. In Aim 1, we will determine how RV exposure modulates agonist-induced
calcium homeostasis in HASM and how asthma alters these mechanisms. Aim 2 will examine how RVC
exposure modulates agonist-induced bronchodilation/relaxation of HASM and how asthma alters these
mechanisms. Utilizing primary HAEC/HASM co-cultures and an ex vivo system of human small airways, we will
delineate signaling pathway alterations regulating bronchomotor tone that can be targeted in the treatment of
RV-induced exacerbations of asthma.

## Key facts

- **NIH application ID:** 10241716
- **Project number:** 1R56HL142890-01A1
- **Recipient organization:** RUTGERS BIOMEDICAL/HEALTH SCIENCES-RBHS
- **Principal Investigator:** Cynthia Koziol-White
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $404,167
- **Award type:** 1
- **Project period:** 2020-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241716

## Citation

> US National Institutes of Health, RePORTER application 10241716, Mechanisms of Rhinovirus-induced airway hyperresponsiveness: an airway smooth muscle perspective (1R56HL142890-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241716. Licensed CC0.

---

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