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NMDAR activation attenuates the protective effect of BM-MSCs on bleomycin-induced ALI via the COX-2/PGE 2 pathway.
- Source :
-
Heliyon [Heliyon] 2023 Dec 19; Vol. 10 (1), pp. e23723. Date of Electronic Publication: 2023 Dec 19 (Print Publication: 2024). - Publication Year :
- 2023
-
Abstract
- N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation mediates glutamate (Glu) toxicity and involves bleomycin (BLM)-induced acute lung injury (ALI). We have reported that bone marrow-derived mesenchymal stem cells (BM-MSCs) are NMDAR-regulated target cells, and NMDAR activation inhibits the protective effect of BM-MSCs on BLM-induced pulmonary fibrosis, but its effect on ALI remains unknown. Here, we found that Glu release was significantly elevated in plasma of mice at d 7 after intratracheally injected with BLM. BM-MSCs were pretreated with NMDA (the selective agonist of NMDAR) and transplanted into the recipient mice after the BLM challenge. BM-MSCs administration significantly alleviated the pathological changes, inflammatory response, myeloperoxidase activity, and malondialdehyde content in the damaged lungs, but NMDA-pretreated BM-MSCs did not ameliorate BLM-induced lung injury in vivo . Moreover, NMDA down-regulated prostaglandin E <subscript>2</subscript> (PGE <subscript>2</subscript> ) secretion and cyclooxygenase (COX)-2 expression instead of COX-1 expression in BM-MSCs in vitro . We also found that NMDAR1 expression was increased and COX-2 expression was decreased, but COX-1 expression was not changed in primary BM-MSCs of BLM-induced ALI mice. Further, the cultured supernatants of lipopolysaccharide (LPS)-pretreated RAW264.7 macrophages were collected to detect inflammatory factors after co-culture with NMDA-pretreated BM-MSCs. The co-culture experiments showed that NMDA precondition inhibited the anti-inflammatory effect of BM-MSCs on LPS-induced macrophage inflammation, and PGE <subscript>2</subscript> could partially alleviate this inhibition. Our findings suggest that NMDAR activation attenuated the protective effect of BM-MSCs on BLM-induced ALI in vivo . NMDAR activation inhibited COX-2 expression and PGE <subscript>2</subscript> secretion in BM-MSCs and weakened the anti-inflammatory effect of BM-MSCs on LPS-induced macrophage inflammation in vitro . In conclusion, NMDAR activation attenuates the protective effect of BM-MSCs on BLM-induced ALI via the COX-2/PGE <subscript>2</subscript> pathway. Keywords : Acute Lung Injury, BM-MSCs, NMDA receptor, COX-1/2, PGE <subscript>2</subscript> .<br />Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (© 2023 The Authors.)
Details
- Language :
- English
- ISSN :
- 2405-8440
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Heliyon
- Publication Type :
- Academic Journal
- Accession number :
- 38205313
- Full Text :
- https://doi.org/10.1016/j.heliyon.2023.e23723