Lipocalin 2 activates the NLRP3 inflammasome via LPS‑induced NF‑κB signaling and plays a role as a pro‑inflammatory regulator in murine macrophages

Kim,Se Lim; Shin,Min Woo; Kim,Sang Wook

doi:10.3892/mmr.2022.12875

Lipocalin 2 activates the NLRP3 inflammasome via LPS‑induced NF‑κB signaling and plays a role as a pro‑inflammatory regulator in murine macrophages

Authors:
- Se Lim Kim
- Min Woo Shin
- Sang Wook Kim
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Affiliations: Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University, Jeonju, Jeonbuk 54907, Republic of Korea
Published online on: October 19, 2022 https://doi.org/10.3892/mmr.2022.12875
Article Number: 358
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lipocalin 2 (LCN2) is highly expressed in several infectious and inflammatory disorders. However, the expression level and underlying mechanism of LCN2 in inflammatory bowel disease (IBD) are poorly understood. The current study used murine IBD models and LPS‑activated macrophages to elucidate the role of LCN2 in IBD pathogenesis. The levels of LCN2 protein and concentration were confirmed to be much higher in the colons of colitis‑induced mice compared with healthy mice using immunohistochemistry, western blotting and ELISA assay. In vitro, the level of LCN2 in RAW264.7 macrophages increased significantly following LPS stimulation and diminished markedly upon using NF‑κB‑specific inhibitors. Assembly of the NOD‑, LRR‑, and pyrin domain‑containing protein 3 (NLRP3) inflammasome was inhibited when LCN2 expression was knocked down, as evidenced by decreased NLRP3, ASC‑1 and caspase‑1 activation. Furthermore, secretion and maturation of IL‑1β was attenuated when LCN2 was silenced in LPS‑stimulated macrophages. Together, these results suggested that LCN2 directly upregulated the NLRP3 inflammasome complex via NF‑κB activation in response to stimulating macrophages with LPS, and that it acted as a pro‑inflammatory regulator in macrophage activation modulated by NF‑κB activation. Overall, LCN2 may serve as a promising target for the prevention and treatment of IBD.

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