Morphine‐induced macrophage apoptosis: the role of transforming growth factor‐β

Abstract

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.

Daily moderate amounts of red wine or alcohol have no effect on the immune system of healthy men

“…The present data show that neither RW nor 12% ETOH at a volume of 500 ml/day affected lymphocyte apoptosis. TGF-b production by LPS-activated monocytes, which has been demonstrated to partly mediate the increase in monocyte apoptosis by ETOH (Singhal et al, 1999b), also did not differ between the beverages.…”

De novo malignancies after liver transplantation: A major cause of late death

“…Although there are many reports of PTLD in LT populations, there are no reports of increased mortality caused by PTLD in liver transplant recipients with ALD. Ethanol has been reported to increase karotypic chromosomal aberrations 51,52 ; expression of TGF-␤ in a variety of cells, including macrophages 53 and liver cells 54 ; and suppression of immunity toward cancer and infections in experimental models. 55,56 This potential enhancement of cancer susceptibility in patients with ALD who underwent LT was also noted in other de novo cancers, with rates of oropharyngeal and lung cancers 25.5 and 3.7 times greater in the ALD group compared with the general population matched for age, sex, and length of follow-up using SEER data, respectively.…”

Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas Ligand

“…Fas system was also supposed to be a key regulator of germ cell apoptosis in testis [10] and up-regulation of Fas ligand was reported in many toxicant-induced testicular germ cell apoptosis [25,26]. In addition, numerous studies showed that apoptosis was an important mechanism by which ethanol caused tissue injury [27,28]. Recently, Zhu et al firstly showednumerous studies showed that apoptosis was an important mechanism by which ethanol caused tissue injury that chronic ethanol exposure enhanced apoptosis of testicular germ cells and measured expression of some apoptosis-related proteins such as Bcl-2, p53 and Fas ligand [19].…”