# Mechanism and targeting of inflammasome activation in lung inflammation and injury

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $571,095

## Abstract

The NLRP3 inflammasome is unique in that it requires a two-step activation process: the priming and the activating. The priming step involves the induction of NLRP3 and pro-IL-1β, whereas the activating step results in the full inflammasome activation triggered by a NLRP3 activator. Although the mechanism leading to the activation of the NLRP3 inflammasome has been increasingly clear, the regulation of this process remains poorly defined. Dysregulation of NLRP3 inflammasome has been frequently implicated in the bacterial pneumonia caused acute lung injury (ALI). MafB is a member of the large MAF transcription factor subfamily and has been implicated in immune disorders, which mainly concerns its role in macrophage apoptosis, phagocytosis and the complement system. In our preliminary studies, we made an unexpected discovery that uncovers a novel function of MafB in regulating the NLRP3 inflammasome activation. Our findings suggest that MafB is a new negative regulator of the NLRP3 inflammasome in vitro and in vivo. We hypothesize that LPS, and P. aeruginosa induced MafB downregulation is a crucial step for the NLRP3 inflammasome priming; MafB is a key player that regulates the NLRP3 inflammasome activation; MafB plays an important role in the pathogenesis of ALI; as well as targeting MafB is an effective therapeutics for ALI. We aim to comprehensively delineate the regulation of MafB expression at the transcriptional and post-translational levels during the NLRP3 inflammasome priming; to delineate the mechanism by which MafB inhibits the NLRP3 inflammasome activation; and to determine the role of MafB in LPS and P. aeruginosa induced acute lung injury (ALI).

## Key facts

- **NIH application ID:** 10657193
- **Project number:** 1R01AI170913-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Gang Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $571,095
- **Award type:** 1
- **Project period:** 2023-02-16 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10657193

## Citation

> US National Institutes of Health, RePORTER application 10657193, Mechanism and targeting of inflammasome activation in lung inflammation and injury (1R01AI170913-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10657193. Licensed CC0.

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