# Control of Macrophage Activation in Lung Disease

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2020 · $603,488

## Abstract

ABSTRACT
 This project will explore how distinct subsets of macrophages moderates inflammation and remodel excess
airway extracellular matrix (ECM) that builds up in response to lung injury. The mechanistic focus will center on
how stromelysin-2 (MMP10), a member of the matrix metalloproteinase family of extracellular endopeptidases,
functions in a cell-autonomous manner to control the activation of immunosuppressive and ECM-degrading
programs in macrophages. Key preliminary data demonstrate that MMP10 is induced in macrophages and
functions to drive their activation status from pro-inflammatory cells (i.e., M1-biased) to immunosuppressive
macrophages (i.e., M2-biased). M2 macrophages are considered to be remodeling competent, and additional
preliminary data demonstrates that MMP10 promotes the activation of an effective remodeling phenotype in
M2 macrophages by regulating the expression of other metalloproteinases with matrix-degrading activity. This
project will test the hypotheses that MMP10 sheds a cell-surface protein on macrophage and that loss of this
protein initiates signaling to turn on immuno-regulatory and ECM-remodeling programs in M2-biased
macrophages. The aims are to 1) determine the role of MMP10 in regulating macrophage activation and
immunosuppressive function in lung fibrosis.; 2) identity the ECM-degrading proteinases controlled by MMP10;
and 3) identify and validate the MMP10 substrate affecting macrophage activation. The approach will include
the use of genetically-defined mouse models, mouse and human cells, and analytical approaches.

## Key facts

- **NIH application ID:** 9898443
- **Project number:** 5R01HL141078-03
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** WILLIAM C PARKS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $603,488
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898443

## Citation

> US National Institutes of Health, RePORTER application 9898443, Control of Macrophage Activation in Lung Disease (5R01HL141078-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9898443. Licensed CC0.

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