IL-1Beta autocrine loop differentially regulates astrocyte inflammatory responses in HAND

Hypothesis: HIV-1 infection of the central nervous system (CNS) impairs brain function and leads to HIV associated neurocognitive disorders (HAND). Astrocytes are the most abundant cell type in CNS and provide structural and metabolic support under homeostasis and in diseases including HAND. It is well established that IL-1beta is regulated in an autocrine fashion. Given our prior work on astrocyte inflammatory responses in HAND, we sought to investigate the role of IL-1beta autocrine loop in differential outcomes. Materials and Methods: Successfully knocking down new synthesis of IL-1beta by RNAi, changes in levels of CXCL-8, TNF-alpha, AEG-1, EAAT-2, TAAR-1 and TIMP-1 were measured in response to IL-1beta stimulation. Astrocytes were infected with the help of doubly fluorescent labelled pseudotyped HIV-1, and latently infected ones were sorted. Results: As expected, RT2-PCR data confirmed that there was an increased mRNA expression of CXCL-8, TNF-alpha, TAAR-1 and TIMP-1 and no changes in EAAT-2 and AEG-1 levels. Conclusions and Future Directions: This suggests that IL-1beta autocrine loop likely plays a differential role in astrocyte inflammatory responses. Furthermore, we are particularly interested in differential response of healthy versus latently HIV-1-infected astrocytes that act as viral reservoir in CNS. Our long term goal is to delineate the specific role of IL-1beta autocrine loop in differential regulation of inflammatory responses in latently infected astrocytes. These studies are highly significant to address CNS reservoir issues in post ART HAND.