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.

Public Health Relevance

COPD is one of the most prevalent comorbidities in older HIV+ patients. We hypothesize that HIV infection causes accelerated epithelial senescence that contributes to the increased incidence of COPD in HIV+ patients. Understanding the mechanisms by which HIV accelerates the development of COPD may lead to new strategies for treatment and prevention of this significant cause of morbidity and mortality in HIV+ patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL120391-01
Application #
8593169
Study Section
Special Emphasis Panel (ZRG1-AARR-K (58))
Program Officer
Caler, Elisabet V
Project Start
2013-08-01
Project End
2015-06-30
Budget Start
2013-08-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$207,060
Indirect Cost
$88,060
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195