Silencing of triggering receptor expressed on myeloid cells-2 enhances the inflammatory responses of alveolar macrophages to lipopolysaccharide
Open accessAbstract
Triggering receptor expressed on myeloid cells-2 (TREM-2) has been shown to attenuate inflammatory responses in various cell lines including bone marrow-derived macrophages, hepatic macrophages, osteoclasts and dendritic cells. However, its effects on alveolar macrophages remain unknown. Lentivirus-mediated RNA interference (RNAi) is a post-transcriptional gene silencing method, which is capable of degrading target genes specifically and efficiently. In this study, we silenced TREM-2 in murine alveolar macrophages by using lentivirus-mediated short hairpin RNA (shRNA) and evaluated the effects of TREM-2 silencing on expression of toll-like receptor-4 (TLR-4), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in response to lipopolysaccharide (LPS). Alveolar macrophages were transfected with shRNA targeting TREM-2 by use of lentivirus vector, non-sense shRNA as a negative control or empty lentivirus vector as a blank control. Silencing of TREM-2 was assessed by real‑time fluorescence quantitative PCR and flow cytometry. Following LPS stimulation, the levels of TLR-4, TNF-α and IL-10 expressed in alveolar macrophages were measured by real-time PCR, flow cytometry or ELISA. TREM-2 expression on alveolar macrophages was downregulated significantly by lentivirus-mediated shRNA treatment at the transcriptional and translational levels. However, alveolar macrophages that received non-sense shRNA or empty lentivirus vectors showed no effects on TREM-2 expression. Silencing of TREM-2 enhanced expression of TLR-4, as well as TNF-α and IL-10, by alveolar macrophages following LPS stimulation. These results indicate a significant effect of TREM-2 on attenuating the LPS-induced inflammatory response of murine alveolar macrophages, which may be dependent on TLR-4.
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TREM2 suppresses LPS-induced pro-inflammatory markers up-regulated in primary alveolar macrophages in vitro and in the BV-2 microglial cell line.
“TREM2 was also found to suppress LPS-induced pro-inflammatory markers up-regulated in primary alveolar macrophages in vitro (28), and the BV-2 microglial cell line (29).”
From <i>Trem2</i> promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [28]
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“TREM2 was also found to suppress LPS-induced pro-inflammatory markers up-regulated in primary alveolar macrophages in vitro (28), and the BV-2 microglial cell line (29).”
BackgroundDevelopment and Functions of Alveolar Macrophages
Woo, Y. D., Jeong, D., & Chung, D. H. (2021) · Molecules and Cells · doi:10.14348/molcells.2021.0058 · Cited by 110 · see citing works
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- Authors
- GAO, X., DONG, Y., LIU, Z., & NIU, B.
- Affiliations
- Shanxi Medical University (CN)
- Venue
- Molecular Medicine Reports
- Publisher
- Spandidos Publications
- Published
- 2013-01-10
- Volume
- 7
- Issue
- 3
- Pages
- 921-926
- ISSN
- 1791-2997 (ISSN-L)
- 1791-3004
- OpenAlex
- W2071108818
- Cited by
- 60
- References
- 20
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 1 · 2022: 6 · 2021: 10 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 3 · 2013: 1
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Medicine Reports (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- TREM2, alveolar macrophages, lipopolysaccharide, inflammation, TLR4, TNF-α, IL-10, gene silencing, shRNA, innate immunity
- MeSH terms
- Animals, Cell Survival, Genetic Vectors, Lipopolysaccharides, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Receptors, Immunologic, Tumor Necrosis Factor-alpha, Up-Regulation, Lentivirus, Macrophages, Alveolar, Interleukin-10, Inflammation Mediators, RNA Interference, RNA, Small Interfering, Toll-Like Receptor 4, Mice
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