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Morphine‐induced macrophage apoptosis: the role of transforming growth factor‐β
Author(s) -
Singhal P. C.,
Kapasi A. A.,
Franki N.,
Reddy K.
Publication year - 2000
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2000.00007.x
Subject(s) - apoptosis , morphine , dna fragmentation , transforming growth factor , cell culture , programmed cell death , fragmentation (computing) , opiate , chemistry , microbiology and biotechnology , endocrinology , biology , medicine , pharmacology , biochemistry , receptor , ecology , genetics
Summary Laboratory and clinical reports indicate that opiate addicts are prone to infections. This effect of opiates is partly attributed to opiate‐induced macrophage (Mφ) apoptosis. In the present study, we evaluated the role of transforming growth factor‐β (TGF‐β) in morphine‐induced apoptosis of murine J774 cells and peritoneal Mφ. Mφ harvested from morphine‐treated mice showed greater ( P < 0·0001) apoptosis when compared with control Mφ. Morphine also enhanced apoptosis of J774 cells and peritoneal Mφ. Anti‐TGF‐β antibody inhibited ( P < 0·001) the morphine‐induced apoptosis in J774 cells (control 0·7 ± 0·4%; 10 −6 m morphine 23·5 ± 0·7%; anti‐TGF‐β antibody (Ab) + 10 −6 m morphine 8·1 ± 0·7%; apoptotic cells/field) and peritoneal Mφ (control 1·5 ± 0·9%; 10 −6 m morphine 29·1 ± 1·4%; 10 −6 m morphine + anti‐TGF‐β Ab 19·1 ± 1·8%; apoptotic cells/field). TGF‐β enhanced ( P < 0·001) apoptosis of J774 cells and peritoneal Mφ. TGF‐β also promoted Mφ DNA fragmentation into integer multiples of 180 bp (ladder pattern). Immunocytochemical studies revealed that morphine enhanced the Mφ cytoplasmic content of TGF‐β. In addition, Western blotting showed increased production of TGF‐β by morphine‐treated J774 cells when compared with control cells. Morphine increased J774 cell expression of bax. Interestingly, morphine‐induced bax expression was inhibited by anti‐TGF‐β Ab. As both morphine‐induced J774 cell apoptosis and bax expression were inhibited by anti‐TGF‐β Ab, it appears that morphine‐induced J774 cell apoptosis may be mediated through the generation of TGF‐β.