Pancreatogenic Diabetes: Triggering Effects of Alcohol and HIV.
Pancreatogenic Diabetes: Triggering Effects of Alcohol and HIV.
复制标题
DOI：
10.3390/biology10020108
复制
发表时间：
2021-02-03
期刊：
影响因子：
4.2
通讯作者：
Osna NA
中科院分区：
文献类型：
--
作者：
New-Aaron M;Ganesan M;Dagur RS;Kharbanda KK;Poluektova LY;Osna NA
你知道吗，尽管有高效抗逆转录病毒治疗（HAART）的效果，艾滋病毒仍可能直接导致器官损伤？由于当前HAART的效力，这可能看起来值得怀疑;然而，过量饮酒可能会增加艾滋病毒引起的器官损伤的风险。虽然胃肠道系统中最受影响的器官是肝脏，但胰腺也可能受到影响。在这项研究中，我们的目的是揭示酒精滥用艾滋病患者胰腺炎的机制，这是制定有效的治疗策略的关键。从文献中，我们发现，酒精诱导的细胞内酶原激活介导的钙和溶酶体水解酶导致腺泡坏死。类似地，HIV进入胰腺腺泡细胞介导ER和氧化应激，其触发腺泡坏死。免疫细胞的浸润也被报道诱导坏死。因此，有效的治疗方案，艾滋病毒和酒精诱导的胰腺炎应抑制艾滋病毒进入和改善酒精对胰腺的毒性作用。尽管使用HAART，但艾滋病毒感染者的多器官衰竭可能无法完全解决。虽然器官功能障碍的可能性可能相对较低，但酒精可能会加强艾滋病毒引起的酒精滥用，艾滋病毒感染者器官的毒性作用。胰腺是最受影响的器官之一，表现为糖尿病或胰腺癌。酒精和艾滋病毒都可能引发胰腺炎，但尚未探讨其联合作用。本文就HIV和酒精引起胰腺毒性的机制进行综述。我们发现，虽然过早的酒精诱导酶原激活是酒精性胰腺炎的已知触发因素，但HIV通过C-C趋化因子受体5型（CCR 5）进入胰腺腺泡细胞也可能导致HIV感染者（PLWH）发生胰腺炎。HIV蛋白诱导氧化和ER应激，引起坏死。此外，浸润性免疫细胞诱导含HIV腺泡细胞坏死。当坏死产物与胰腺星状细胞相互作用时，它们被激活，导致炎症和促纤维化细胞因子的释放，并导致胰腺炎。有效的治疗策略应该阻断CCR 5，改善酒精对腺泡细胞的影响。
Did you know that HIV may directly cause organ damage despite the effects of highly active antiretroviral therapy (HAART)? Due to the potency of current HAART, this may look questionable; however, excessive alcohol use may increase the risk of HIV-induced organ damage. While the most implicated organ in the gastrointestinal system is the liver, the pancreas may also be affected. In this study, we aimed to disclose the mechanisms of pancreatitis in alcohol-abusing HIV patients, which is crucial for developing an effective therapeutic strategy. From the literature, we found that alcohol-induced intracellular zymogen activation was mediated by calcium and lysosome hydrolases leading to acinar necrosis. Similarly, HIV entry into pancreatic acinar cells mediates ER and oxidative stress, which triggers acinar necrosis. Infiltration of immune cells has also been reported to induce necrosis. Therefore, effective therapeutic regimens for HIV and alcohol-induced pancreatitis should inhibit HIV entry and ameliorate alcohol’s toxic effects on the pancreas. Multiorgan failure may not be completely resolved among people living with HIV despite HAART use. Although the chances of organ dysfunction may be relatively low, alcohol may potentiate HIV-induced toxic effects in the organs of alcohol-abusing, HIV-infected individuals. The pancreas is one of the most implicated organs, which is manifested as diabetes mellitus or pancreatic cancer. Both alcohol and HIV may trigger pancreatitis, but the combined effects have not been explored. The aim of this review is to explore the literature for understanding the mechanisms of HIV and alcohol-induced pancreatotoxicity. We found that while premature alcohol-inducing zymogen activation is a known trigger of alcoholic pancreatitis, HIV entry through C-C chemokine receptor type 5 (CCR5) into pancreatic acinar cells may also contribute to pancreatitis in people living with HIV (PLWH). HIV proteins induce oxidative and ER stresses, causing necrosis. Furthermore, infiltrative immune cells induce necrosis on HIV-containing acinar cells. When necrotic products interact with pancreatic stellate cells, they become activated, leading to the release of both inflammatory and profibrotic cytokines and resulting in pancreatitis. Effective therapeutic strategies should block CCR5 and ameliorate alcohol’s effects on acinar cells.
登录
查看更多内容
CCR2/5信号的药理抑制可防止和逆转小鼠酒精诱导的肝损伤，脂肪变性和炎症。
DOI：
10.1002/hep.30249
发表时间：
2019-03
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Ambade A;Lowe P;Kodys K;Catalano D;Gyongyosi B;Cho Y;Iracheta-Vellve A;Adejumo A;Saha B;Calenda C;Mehta J;Lefebvre E;Vig P;Szabo G
通讯作者：
Szabo G
影响因子：
5.4
作者：
Brundu, Serena;Palma, Linda;Fraternale, Alessandra
通讯作者：
Fraternale, Alessandra
影响因子：
2.3
作者：
Apte, MV;Pirola, RC;Wilson, JS
通讯作者：
Wilson, JS
DOI：
10.1111/j.1365-2362.2006.01599.x
发表时间：
2006-02-01
影响因子：
5.5
作者：
Asaumi, H;Watanabe, S;Otsuki, M
通讯作者：
Otsuki, M
影响因子：
3.6
作者：
Blauer, Merja;Laaninen, Matias;Laukkarinen, Johanna
通讯作者：
Laukkarinen, Johanna