# Air pollution disrupts Inflammasome Regulation in HEart And Lung Total Health (AIRHEALTH)

> **NIH NIH P01** · STANFORD UNIVERSITY · 2022 · $2,119,953

## Abstract

ABSTRACT: OVERALL COMPONENT Exposure to air pollution from automobile exhaust and forest fires is a
significant, rapidly growing global public health burden that contributes to cardiopulmonary pathogenesis.
Produced by epithelial and inflammatory cells, interleukin-1 beta (IL-1β) is key to this inflammatory response
within blood, lung, cardiac, and vascular tissues, and primarily associated with acute and chronic inflammation
upon exposure to pollutants. Accordingly, understanding the mechanisms of the IL-1β and other pathways will
significantly benefit cardiopulmonary health since therapies are available to block this pathway and since
knowledge of direct mechanisms of how air pollution leads to cardiopulmonary diseases is needed to shape
policy in public health. Our central objective is to test distinct but intertwined mechanistic aspects of IL-1β and
other pathway regulation in inflammation-associated cardiopulmonary pathology linked to air pollution. We will
test the hypothesis that the immunopathology of cardiovascular and pulmonary diseases are linked to IL-1β
and/or other pathways, as we have preliminary data demonstrating activation of IL-1β and inflammasome, and
other pathways in air pollution exposure, particularly PM2.5. We understand there are other pathways other than
IL-1β involved and to this end, we have proposed unbiased, agnostic experiments in all projects and cores,
especially the systems biology approach of project 2. Furthermore, our data show the link of immune pathways
to clinical outcomes, such as increase systolic blood pressure, in young children and adolescents exposed to air
pollution. We have created synergy and dependency of all the projects and cores since we use all the same
samples from the same cohorts, we share data to be able to create composite biological biomarkers to link
pathology to disease (i.e. asthma or increased blood pressure). As an example of our innovation together, we
have proposed using induced pluripotent stem cells (iPSCs) in both lung and heart models (Projects 1 and 3)
to screen and identify agents that block IL-1β and other pathway effects. Our aims are: 1. Describe the
mechanisms underlying heart, lung, and immune diseases associated with air pollution (PM2.5) exposure.
We will identify and characterize biomarkers of acute and chronic environmental exposure to air pollution that
predict cardiopulmonary diseases. 2. Ensure the efforts of the three scientific projects and project cores
will be synergistic, coordinated, and integrated. We describe specifically how the three projects and cores
are synergistic and how we will integrate our study findings with other efforts to investigate IL-1β and other
pathways. 3: Provide a highly interactive, collaborative, and multi-disciplinary team of investigators and
resources to support our goals. We describe our multi-disciplinary facilities and investigators that will
contribute to the overall success of the PPG, called AIRHEALTH. If our program and ...

## Key facts

- **NIH application ID:** 10460326
- **Project number:** 5P01HL152953-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Kari C. Nadeau
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,119,953
- **Award type:** 5
- **Project period:** 2021-08-01 → 2023-01-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460326

## Citation

> US National Institutes of Health, RePORTER application 10460326, Air pollution disrupts Inflammasome Regulation in HEart And Lung Total Health (AIRHEALTH) (5P01HL152953-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10460326. Licensed CC0.

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