B33-03 Synergistic Inflammatory Crosstalk Between the Lung Adipose Tissue Axis on HIV and Cigarette Smoke Exposure

Abstract Background Chronic obstructive pulmonary disease (COPD) has a higher incidence in people living with HIV (PLWH) when compared to the general population. HIV itself risks developing COPD and this is exacerbated by cigarette smoke exposure. Our previous studies demonstrated that TGF-β1 increases viral replication and promotes HIV-1 latency in airway epithelial cells. The combination of antiretroviral therapy (cART) to achieve 85% to 95% of HIV viral suppression but incapable of eradicating HIV due to presence of latently infected anatomical reservoirs. Both lung and adipose tissue can serve as an anatomical HIV reservoir. However, in PLWH dysregulated lipid metabolism and adipose inflammation contribute to chronic lung disease, even with effective antiretroviral therapy. This study focuses on the pathophysiological mechanism of lung inflammation and white adipose tissue (WAT) axis as an emerging insight in HIV-associated COPD comorbidity. Methods Experiments were performed using lungs and white adipose tissue from the SP-C Tat transgenic mice, CS-exposed with SP-C Tat mice lungs, and their WT littermates as a control. Total RNA was analyzed from the lungs and adipose tissue by qRT-PCR. Paired tissues samples were lysed using RIPA buffer containing protease inhibitor cocktail and used for proteomic analysis. Results The SP-C Tat transgenic mice lungs and WAT show that HIV primary receptor CD4 and chemokine receptor-5 (CCR5) are highly expressed with increased expression of proinflammatory cytokines compared to WT littermates. Moreover, it is exacerbated in CS-exposed mice compared to WT mice lungs and adipose tissue. The proteomics data reveals enhanced proinflammatory cytokine proteins in SP-C Tat mice lungs and adipose tissue compared WT mice. In addition, cigarette smoked SP-C Tat mice increased proinflammatory cytokine proteins level were observed compared with SP-C Tat mice alone. Conclusions Our data indicates that HIV primary receptor CD4 and chemokine receptor-5 is highly expressed in both lungs and adipose tissue. We noticed upregulation of several proinflammatory cytokine genes in both lungs and adipose tissue when compared with WT littermate controls. However, cigarette smoke exposed SP-C Tat mice demonstrate synergistic upregulation of inflammatory cytokines with potential effects on COPD development. Hence, identifying the pathophysiological mechanism underlying the interplay between lung and adipose tissue might be a novel therapeutic vector for HIV-associated COPD. This abstract is funded by: NIH