Morphine Enhances LPS-induced Macrophage Apoptosis Through a PPARγ-dependent Mechanism

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2021 May 19

PMID 34007323

Citations 4

Authors

Mingying Lin

Keqiong Deng

Ya Li

Jing Wan

Affiliations

Soon will be listed here.

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 and 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.

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