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Morphine-induced macrophage apoptosis: the role of transforming growth factor-beta
P C Singhal1, A A Kapasi, N Franki
1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.
Abstract:
Laboratory and clinical reports indicate that opiate addicts are prone to infections. This effect of opiates is partly attributed to opiate-induced macrophage (Mphi) apoptosis. In the present study, we evaluated the role of transforming growth factor-beta (TGF-beta) in morphine-induced apoptosis of murine J774 cells and peritoneal Mphi. Mphi harvested from morphine-treated mice showed greater (P < 0. 0001) apoptosis when compared with control Mphi. Morphine also enhanced apoptosis of J774 cells and peritoneal Mphi. Anti-TGF-beta 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-beta antibody (Ab) + 10-6 M morphine 8.1 +/- 0.7%; apoptotic cells/field) and peritoneal Mphi (control 1.5 +/- 0.9%; 10-6 M morphine 29.1 +/- 1.4%; 10-6 M morphine + anti-TGF-beta Ab 19. 1 +/- 1.8%; apoptotic cells/field). TGF-beta enhanced (P < 0.001) apoptosis of J774 cells and peritoneal Mphi. TGF-beta also promoted Mphi DNA fragmentation into integer multiples of 180 bp (ladder pattern). Immunocytochemical studies revealed that morphine enhanced the Mphi cytoplasmic content of TGF-beta. In addition, Western blotting showed increased production of TGF-beta 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-beta Ab. As both morphine-induced J774 cell apoptosis and bax expression were inhibited by anti-TGF-beta Ab, it appears that morphine-induced J774 cell apoptosis may be mediated through the generation of TGF-beta.
Insights
Morphine induces macrophage apoptosis, increasing infection risk in opiate addicts. This study reveals transforming growth factor-beta (TGF-beta) mediates this effect, suggesting therapeutic targets for immune dysfunction.
Area of Science:
- Immunology
- Pharmacology
Background:
- Opiate addiction is linked to increased infection susceptibility.
- Opiate-induced macrophage (Mphi) apoptosis is a key factor in this immune suppression.
Purpose of the Study:
- To investigate the role of transforming growth factor-beta (TGF-beta) in morphine-induced Mphi apoptosis.
- To elucidate the molecular mechanisms underlying morphine's impact on immune cells.
Main Methods:
- Assessed Mphi apoptosis in morphine-treated mice and cell cultures.
- Utilized anti-TGF-beta antibodies to block TGF-beta's effects.
- Examined TGF-beta and bax expression via immunocytochemistry and Western blotting.
Main Results:
- Morphine significantly increased Mphi apoptosis, which was reduced by anti-TGF-beta antibody.
- TGF-beta alone enhanced Mphi apoptosis and DNA fragmentation.
- Morphine elevated TGF-beta and bax expression in Mphi, with bax inhibition by anti-TGF-beta antibody.
Conclusions:
- TGF-beta plays a critical role in mediating morphine-induced Mphi apoptosis.
- Morphine-induced apoptosis may involve the TGF-beta/bax pathway.
- Targeting TGF-beta could mitigate opiate-induced immune suppression.