Impact of HIV Infection on Cellular Senescence and Potential Role in COPD Pathoge

描述：COPD是HIV+患者中最常见的并存疾病之一，在老年HIV+患者中更为常见。越来越多的研究表明，上皮细胞加速衰老在COPD的发生发展中起着重要作用。衰老不仅会损害细胞重新填充受损呼吸道的能力，还会通过分泌炎性细胞因子和生长因子而导致肺部疾病，这种细胞因子和生长因子被称为衰老相关分泌表型(SASP)。到目前为止，艾滋病毒感染在肺部细胞过早衰老中的作用尚不清楚。我们假设HIV感染会加速上皮细胞的衰老，最终导致COPD的过早发展。为了开始解决这个问题，我们将检查来自HIV+患者的支气管肺泡灌洗(BAL)是否富含SASP标志物，并且与来自HIV患者的BAL相比，是否可以诱导原代肺上皮细胞衰老。同时，我们将研究HIV感染的淋巴细胞或巨噬细胞是否在体外诱导肺上皮细胞衰老。这些研究将填补我们知识的空白，因为人们对艾滋病毒感染对细胞衰老发展的影响知之甚少。这些结果将为未来研究细胞衰老对HIV+患者COPD加速发展的贡献提供基础。

DESCRIPTION: COPD is one of the most prevalent comorbidities in HIV+ patients and is substantially more common in older HIV+ patients. An increasing number of studies have demonstrated a role of accelerated epithelial senescence in the development of COPD. Senescence can contribute to lung disease not only by impairing the ability of cells to repopulate an injured airway, but by secretion of inflammatory cytokine and growth factors, known as the "senescence-associated secretory phenotype (SASP). To date, a role of HIV infection in premature cellular senescence in the lung is unexplored. We hypothesize that HIV infection accelerates epithelial senescence, which ultimately predisposes to the premature development of COPD. To begin to address this question, we will examine whether bronchoalveolar lavage (BAL) from HIV+ patients is enriched with markers of SASP, and can induce senescence of primary lung epithelial cells compared to BAL from HIV- patients. In parallel, we will examine whether HIV-infected lymphocytes or macrophages induce lung epithelial senescence in vitro. These studies will fill gaps in our knowledge since very little is known about the consequences of HIV infection on the development of cellular senescence. These results will provide the foundation for future studies examining the contribution of cellular senescence to accelerated development of COPD in HIV+ patients.