Wednesday, May 19, 2021

Morphine enhances LPS-induced macrophage apoptosis through a PPARγ-dependent mechanism

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Exp Ther Med. 2021 Jul;22(1):714. doi: 10.3892/etm.2021.10146. Epub 2021 May 3.

ABSTRACT

Morphine has been widely used for the treatment of pain and extensive studies have revealed a regulatory role for morphine in cell apoptosis. However, the molecular mechanisms underlying morphine-mediated apoptosis remain to be fully elucidated. The present study aimed to investigate the effects of morphine on lipopolysaccharide (LPS)-induced bone marrow-derived macrophage (BMDM) apoptosis and to determine the role of the peroxisome proliferator-activated receptor (PPAR)γ signaling pathway in this process. BMDMs were isolated from BALB/c mice and stimulated with LPS. Hoechst 33342 staining and flow cytometric analysis were performed to evaluate the effects of morphine on LPS-induced apoptosis of BMDMs. Caspase activity assays were used to determine the involvement of the apoptosis pathway. The expression levels of caspase-3, caspase-8, caspase-9 a nd PPARγ were analyzed using western blotting. Finally, GW9662, a specific PPARγ antagonist, was used to determine whether the regulatory effects of morphine on LPS-induced BMDM apoptosis were PPARγ-dependent. The results of the present study revealed that morphine increased the apoptosis of LPS-stimulated BMDMs. Morphine upregulated the expression levels and activity of caspase-3 in LPS-stimulated BMDMs, but downregulated the expression levels and activity of caspase-8. Morphine treatment also upregulated LPS-induced PPARγ expression levels in BMDMs. Finally, the stimulatory effects of morphine on LPS-induced apoptosis and caspase-3/9 activation were markedly reduced by GW9662. In conclusion, the findings of the present study indicated that morphine significantly promoted LPS-induced BMDM apoptosis and caspase-3/9 activation. These results suggested that the intrinsic pathway of apoptosis may be involved in the proapoptotic effects of morphine on LPS-stimulated BMDMs, which may be dependent, at least partially, on PPARγ activation.

PMID:34007323 | PMC:PMC8120503 | DOI:10.3892/etm.2021.10146

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