# LncRNA regulates lung inflammation

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $491,584

## Abstract

ABSTRACT
 Lung infections place a major burden on public health worldwide and are the leading cause of death in the
United States. Infections caused by gram-negative (G-) bacteria have features that are of particular concern,
such as being highly efficient at acquiring antibiotic resistance. Alveolar macrophages (AMs) form the first line
of defense in lungs toward microbial pathogens via protective inflammatory responses. The high mortality and
morbidity after bacterial infection often result from an imbalance in host defense between bactericidal and an
excessive inflammatory response that leads to tissue damage. Despite years of research, the initiation,
propagation and regulation of inflammatory lung responses in the presence of G- bacterial infection remains
incompletely explored. Only recently has it been recognized that long non-coding RNAs (lncRNA) are
extensively expressed in various immune cells including the macrophages, but very little has been known about
their functional roles. We screened lncRNA expressions in mouse lungs after intra-tracheal instillation of LPS,
Klebsiella pneumoniae (K.pneumoniae) and Escherichia coli (E.coli). LncRNA lincenc1 exhibited the greatest
induction in expression among treated groups. Functionally, lincenc1 promotes the classical activation (M1) of
macrophages and the secretion of pro-inflammatory cytokines. Deletion of lincenc1 in AMs using the specific
antisense oligonucleotides (ASO) in vivo significantly reduces the LPS-induced leukocyte infiltration and alveolar
edema, when compared with the control group. Furthermore, inhibition of lincenc1 using ASO down-regulates
multiple inflammatory cytokines and chemokines (Il-1β, Il-6, Cxcl1 and Cxcl2), detected in BALF after exposure
to LPS. Mechanistically, we found that lincenc1 co-localizes with NLRP3 components in the presence of LPS,
suggesting a regulatory role of lincenc1 on NLRP3 inflammasone activation. Based on our published and
preliminary data, our central hypothesis is that lncRNA lincenc1 facilitates G-bacteria/LPS induced lung
inflammation via promoting classical activation of macrophages through NLRP3 inflammasome assembly and
activation. We propose three specific aims: Specific Aim I: To determine the role of lncRNA lincenc1 in
macrophage activation in vitro. Specific Aim II: To determine the role of lincenc1 in lung inflammation in vivo.
Specific Aim III: To determine whether lincenc1 serves as a potential therapeutic target in vivo.

## Key facts

- **NIH application ID:** 10001992
- **Project number:** 5R01HL142758-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Yang Jin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $491,584
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001992

## Citation

> US National Institutes of Health, RePORTER application 10001992, LncRNA regulates lung inflammation (5R01HL142758-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001992. Licensed CC0.

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