Effect of Cocaine on HIV Infection and Inflammasome Gene Expression Profile in HIV Infected Macrophages

Abstract

We have observed significantly increased HIV infection in HIV infected macrophages in the presence of cocaine that could be due to the downregulation of BST2 restriction factor in these cells. In human inflammasome PCR array, among different involved in inflammasome formation, in HIV infected macrophages in the presence of cocaine, we have observed significant upregulation of NLRP3, AIM2 genes and downstream genes IL-1β and PTGS2. Whereas negative regulatory gene MEFV was upregulated, CD40LG and PYDC1 were significantly downregulated. Among various NOD like receptors, NOD2 was significantly upregulated in both HIV alone and HIV plus cocaine treated cells. In the downstream genes, chemokine (C-C motif) ligand 2 (CCL2), CCL7 and IL-6 were significantly up regulated in HIV plus cocaine treated macrophages. We have also observed significant ROS production (in HIV and/or cocaine treated cells) which is one of the indirect-activators of inflammasomes formation. Further, we have observed early apoptosis in HIV alone and HIV plus cocaine treated macrophages which may be resultant of inflammasome formation and cspase-1 activation. These results indicate that in case of HIV infected macrophages exposed to cocaine, increased ROS production and IL-1β transcription serve as an activators for the formation of NLRP3 and AIM2 mediated inflammasomes that leads to caspase 1 mediated apoptosis.

Crucial biological functions of CCL7 in cancer

“…As a chemotactic factor, CCL7 recruits a leukocyte subtype to infected tissues to address pathologic invasion and fine-tune the immune response. However, abnormal increase of CCL7 exacerbates the deterioration of various disorders, like lesional psoriasis ( Brunner et al, 2015 ), acquired immunodeficiency syndrome ( Atluri et al, 2016 ), acute neutrophilic lung inflammation and pulmonary fibrosis ( Choi et al, 2004 ; Mercer et al, 2014 ). More recently, the autocrine and paracrine roles of CCL7 in cancer progression have received increasing attention, although the potential molecular cues involved are incompletely understood.…”

Role of Inflammasomes in HIV-1 and Drug Abuse Mediated Neuroinflammaging

“…Together these studies provide evidence for the role of the NLRP3 inflammasome during HIV-1 infection. In the context of drug abuse, cocaine has been shown to upregulate the expression levels of NLRP3 in macrophages infected with HIV-1 [ 98 ]. The production of reactive oxygen species (ROS) was also increased in cocaine-exposed macrophages, thus suggesting an upstream role for ROS in cocaine-mediated priming of the NLRP3 inflammasome.…”

“…AIM2 plays a role in the responses to viruses, including HIV-1. In one study, HIV-1 infected macrophages exposed to cocaine exhibited significant upregulation of AIM2 mRNA and IL1β [ 98 ].…”

Development of Multifunctional Biopolymeric Auto-Fluorescent Micro- and Nanogels as a Platform for Biomedical Applications

“…PBMCs were purified from human leukopacks (buffy coat), which were obtained commercially from the community blood bank (One Blood, Miami, FL, United States). PBMCs were isolated as previously described by us (Atluri et al, 2016). The first step involved the dilution of the buffy coat with phosphate buffer saline (PBS) (Invitrogen, Gaithersburg, MD, United States) at room temperature.…”