# Lysosomal BK channel regulates cSiO2-induced macrophage inflammation

> **NIH NIH R21** · UNIVERSITY OF MONTANA · 2022 · $222,000

## Abstract

Abstract
Chronic inflammation is a significant contributing factor to pulmonary and other diseases. One trigger of chronic
inflammation is respirable crystalline silica (cSiO2) in occupational settings, and, therefore, presents a useful
model to investigate the mechanisms of unresolved, lysosome dysfunction-mediated inflammation. cSiO2 causes
phagolysosomal membrane permeabilization (LMP) and NLRP3 inflammasome activation in alveolar
macrophages. Activated inflammasome triggers inflammation through caspase-1 mediated maturation of
interleukin 1b (IL-1b) and interleukin 18 (IL-18). The lysosome’s role in NLRP3 inflammasome activity and its
contributions to macrophage homeostasis make it of significant interest in the development of therapeutic targets
for chronic inflammatory human health conditions. Within the lysosome, ion channels are indispensable to its
function. This research will investigate the role of the lysosomal potassium (K+) channel in LMP and how it
contributes to NLRP3-mediated inflammation. Current literature shows that particulate-induced NLRP3
inflammasome activity correlates to a decrease in cytosolic K+, which is assumed to be K+ efflux from the cytosol
to the extracellular matrix. However, the contribution of lysosomal K+ channels to the decrease of cytosolic K+ in
NLPR3 inflammasome activation will be evaluated in this study. Our preliminary results indicate that K+
movement into the lysosome through the lysosomal big conductance potassium (BK) channel precedes LMP
and NLRP3 inflammasome activity. Blocking lysosomal BK channel activity reduces cSiO2-induced cell death
and IL-1b release, suggesting lysosomal ion channel involvement in the mechanisms in LMP. This project will
address the hypothesis that cSiO2 interacts with the lysosomal membrane and initiates changes in the lysosomal
membrane lipid order and promotes lysosomal BK channel activity, a decrease in cytosolic K+, LMP, and NLRP3
inflammasome activity.

## Key facts

- **NIH application ID:** 10463030
- **Project number:** 1R21ES033511-01A1
- **Recipient organization:** UNIVERSITY OF MONTANA
- **Principal Investigator:** Andrij Holian
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $222,000
- **Award type:** 1
- **Project period:** 2022-05-05 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463030

## Citation

> US National Institutes of Health, RePORTER application 10463030, Lysosomal BK channel regulates cSiO2-induced macrophage inflammation (1R21ES033511-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10463030. Licensed CC0.

---

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