Dataset Information

The role of lipocalin-2 in lung homeostasis, inflammation response, and recovery following organic dust exposure

ABSTRACT: Agricultural industry workers are frequently exposed to harmful dust particles and consequently have a higher risk of developing chronic lung inflammatory conditions such as chronic obstructive pulmonary disease (COPD). Lipocalin-2 (LCN-2) is an innate immune protein with paradoxical roles in both pro- and anti-inflammatory responses at mucosal sites; however, its role in the lung during homeostatic and inflammatory states, such as those induced by inhaled dusts, remain unknown. Here, we investigated the role of LCN-2 in a murine model of organic dust exposure-induced lung inflammation using wildtype C57Bl/6 (WT) and LCN-2 knockout (KO) mice exposed repetitively to extracts of dusts (DE) collected from swine confinement facilities. Repetitive DE exposure consisted of fifteen days of intranasal instillations with and without a three-day recovery period. Through these investigations, we identified an important function of LCN-2 in regulating tissue homeostasis and recovery following inflammatory injury in the lung. Additionally, compartmentalized effects on T cell and macrophage levels were observed in BALF vs. lung tissue in DE-exposed LCN-2 KO mice versus WT mice. Ablation of LCN-2 resulted in deficits in resolving histopathological markers of inflammation, and decreased levels of IL-10 after DE. Exogenous IL-10 administration partially rescued the histopathological markers of inflammation in LCN-2 KO mice after DE exposure. Taken together, these investigations highlight a novel role for LCN-2 in regulating lung homeostasis, inflammation response, and repair following organic dust-induced inflammation that may be mediated, at least in part, by IL-10.

ORGANISM(S): Mus musculus

PROVIDER: GSE254514 | GEO | 2026/06/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Environmental lipopolysaccharide (LPS) and microbial component-enriched organic dusts cause significant lung diseases. These environmental exposures induce the recruitment and activation of distinct lung monocyte/macrophage subpopulations involved in disease pathogenesis. Given monocyte/macrophage activation is tightly linked to metabolism, the objective of these studies was to determine the role of the immunometabolic regulator, aconitate decarboxylase 1 (ACOD1), in environmental exposure-induced lung inflammation. Methods: Wild-type (WT) mice were intratracheally instilled (I.T.) with 10 ug LPS or saline. Whole lungs were profiled using bulk RNA sequencing or sorted to isolate monocyte/macrophage subpopulations. Sorted subpopulations were then characterized transcriptomically using a NanoString innate immunity multiplex array 48 hours post-exposure. Next, WT and Acod1-/- mice were instilled with LPS, 25% organic dust extract (ODE), or saline with serum, bronchoalveolar lavage fluid (BALF), and lung tissues collected. BALF metabolites of the tricarboxylic acid (TCA) cycle were quantified by mass-spectrometry. Cytokines/chemokines and tissue remodeling mediators were quantitated by ELISA. Lung immune cells were characterized by flow cytometry. Whole body plethysmography was performed 3 hours post-LPS with WT and Acod1-/- mice. Results: By bulk sequencing, Acod1 was one of the most significantly upregulated genes following LPS (vs. saline) exposure of murine whole lungs. Transcriptomic profiling of sorted lung monocyte/macrophage subpopulations corroborated Acod1 significance. Acod1-/- mice treated with LPS (vs. WT) demonstrated decreased BALF levels of itaconate, TCA cycle reprogramming, decreased BALF neutrophils, increased lung CD4+ T cells, decreased BALF and lung levels of TNF-a, and decreased BALF CXCL1. In comparison, Acod1-/- mice treated with ODE (vs. WT) demonstrated decreased serum pentraxin-2, BALF levels of itaconate, lung total cell, neutrophil, monocyte, and B cell infiltrates with decreased BALF levels of TNF-a, IL-6, and decreased lung CXCL1. Mediators of tissue remodeling (TIMP1, MMP8, MMP9) were also decreased in the LPS-exposed Acod1-/- mice, with MMP-9 also decreased in the ODE-exposed Acod1-/- mice. Lung function assessments demonstrated a blunted response to LPS-induced airway hyper-responsiveness in Acod1-/- mice. Conclusion: Acod1 is robustly upregulated in the lungs following LPS-exposure and encodes a key immunometabolic regulator. ACOD1 mediates the pro-inflammatory response to acute inhaled, environmental LPS and organic dust exposure-induced lung inflammation.

Dataset Information

The role of lipocalin-2 in lung homeostasis, inflammation response, and recovery following organic dust exposure

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets