The Study On CCR5Expression Induced By Morphine

AIDS is caused by human immunodeficiency virus(HIV). There are about780thousand people infected with HIV/AIDS in China in2011.The blood taken and blood donation, transfusion of blood or blood products transmission accounted for6.6%, the injection drug use transmission accounted for28.4%. Yunnan is the heavy disaster area of AIDS, in1986the first case of AIDS was found,1989-1994, HIV/ADIS are detected in injection drug users in Yunnan. Injection drug use is the major pathway of HIV transmission., thus HIV antibody positive rate is still high.HIV infects human body, specific infects CD4+T cells. The V3area of outer membrane protein gpl20binds to target cell surface CD4and induces gpI20subunit configuration change which exposes coreceptor binding site. Since CD4binding to gpl20only induces conformational changes, can not affect transmembrane proteins, HIV must use the C-C chemokine receptor5(CCR5), the C-X-C chemokine receptor type4(CXCR-4) binding to expose V3area and transmembrane protein gp41from the surface of HIV and infects host target cell. HIV entries to target cells by using different coreceptors in different stages of infection, during the early phase of infection HIV is mainly dependent on CCR5, the latter is to CXCR4as the main coreceptor. Therefore, CCR5as the HIVearly infection coreceptor has attracted researcher’s attention. HIV can cause human immunodeficiency, after infection lifelong lurks in the human body, it can destroy the body’s T lymphocytes lead organs and tissues to be infected. There are currently no effective treatment methods on HIV. CCR5antagonists prevent virus from entrying and infecting immune cells by blocking CCR5cell surface receptors. CCR5antagonists bind to the transmembrane helices of CCR5receptor, then formed the hydrophobic pocket, finally the receptor function is prohibited. CCR5antagonists against HIV infection of T lymphocytes could be considered effective drugs for AIDS.Opioids have roles in inhibiting the immune system, drug addicts have low overall immune function, injection drug using increases susceptibility to HIV. In addition, sharing syringes high frequency of injection drug user, and deficiency AIDS knowledge of drug abusers cause the HIV higher rate infection in drug abusers. In the immune system of drug abusers, losing of the ability of immune cell killing pathogens, and immune material deficiency,such as humoral antibody, interferon, result in decreased immune function, enhance susceptivity to the HIV infection, especially among injecting drug users with syringe needle, syringe needle is not disposable, mostly is not disinfection, once the injection apparatus with HIV, the virus can be inputted to body, causes AIDS.Morphine belongs to the opioid molecules, with quinoline as the core ring molecule can be extracted from the poppy. Effects of morphine on body function are mainly dependent on the opioid receptor, it is widely used in clinical practice for a class of analgesic drugs, long-term use of morphine will cause the action of tolerance, addiction. Therefore, the effects of morphine addiction, limit its widespread application in clinical.Thioredoxin (Trx) is a12KDa protein, has a conservative redox active site sequence: Cys-Gly-Pro-Cys. Trx and reduced nicotinamide adenine dinucleotide phosphate (NADPH) and thioredoxin reductase (TrxR) composed of Trx reduction system. Trx has many biological functions, such as antioxidation, resistance to apoptosis, growth factors and regulation of transcription factor activity. Trx is low expression in early AIDS, high expression in advanced AIDS.In our study, in vitro Trx and CCR5expression induced by morphine in natural CD4+T cells (Jurkat cells) are detected, as well as proinflammatory cytokine TNF-a and anti-inflammation factor IL-10are detected. Experimental results are following:morphine via opioid receptor inhibited Trx, induced expression of CCR5in Jurkat cells, suggesting that CCR5increased opportunity that HIV infected CD4+T. High dose of morphine stimulated Jurkat cell, decreased cell viability, and activated caspase-3s after24h, indicating high dose of morphine induced T cell apoptosis. With the increased concentration of morphine, anti-inflammation factor IL-10increased, TNF-a reduced. In vivo, both acute and chronic morphine treatments on C57BL/6mice, Trx expression was increased in spleen; the acute morphine treatment in mice, there are no effects on CCR5and caspase-3in spleen; and when chronic morphine treatment in mice, in spleen the expression of CCR5was increased, caspase was also activated, suggesting that chronic morphine treatment increases CCR5expression that help HIV infect T lymphocytes receptor, and might induce immune cells apoptosis in spleen. Through the comparing Trx, CCR5, TNF-a and IL-10of normal persons and drug addicts in peripheral blood, peripheral Trx, TNF-a and IL-10decreased significantly, while CCR5expression was significantly increased, indicating that the immune system of drug addicts are damage, increased the expression of CCR5, increased probability of drug addicts infected with HIV.The above results indicate:CCR5plays an important role in addiction medicine induced immune response. Long term effect of morphine can result in CD4+T cell apoptosis and immune factors reduced, resulting in immune function damage. Study on the molecular mechanism of CCR5induced by morphine and mechanism of decreased immune function, will provide a new theoretical basis for the prevention of drug addicts infected with HIV, provide the basic theory of data with the prevention of HIV infection. The peripheral blood of drug addicts in CCR5expression closely related to differences with the susceptibility to HIV and the progress of the disease.The detection of the expression of CCR5in the peripheral blood has certain clinical significance on the early diagnosis, treatment and prognosis in AIDS.