The role of lipocalin-2 in lung homeostasis, inflammation response, and recovery following organic dust exposure
- 1Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California, United States of America
- 2Department of Pediatrics, School of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
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 bronchoalveolar lavage fluid (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 indicators 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.
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BibTeX
@article{guardado2026role,
title = {{The role of lipocalin-2 in lung homeostasis, inflammation response, and recovery following organic dust exposure}},
author = {Stephanie Guardado and Daniel Ojeda-Juárez and Arzu Ulu and Stefanie Sveiven and Edward C. Dominguez and Sang Yong Kim and Shaiva Patel and Marcus Kaul and Tara M. Nordgren},
journal = {PLOS One},
year = {2026},
month = nov,
doi = {10.1371/journal.pone.0359338},
url = {https://doi.org/10.1371/journal.pone.0359338},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The role of lipocalin-2 in lung homeostasis, inflammation response, and recovery following organic dust exposure
AU - Stephanie Guardado
AU - Daniel Ojeda-Juárez
AU - Arzu Ulu
AU - Stefanie Sveiven
AU - Edward C. Dominguez
AU - Sang Yong Kim
AU - Shaiva Patel
AU - Marcus Kaul
AU - Tara M. Nordgren
PY - 2026
DA - 2026/11/03
JO - PLOS One
DO - 10.1371/journal.pone.0359338
UR - https://doi.org/10.1371/journal.pone.0359338
AB - 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 bronchoalveolar lavage fluid (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 indicators 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.
SN - 1932-6203
ER -