Effect of Cocaine on HIV Infection and Inflammasome Gene Expression Profile in HIV Infected Macrophages.
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.
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL-33199, USA.
Venkata Subba Rao
VS
Atluri
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL-33199, USA.
Sudheesh
S
Pilakka-Kanthikeel
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL-33199, USA.
Gabriella
G
Garcia
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL-33199, USA.
Rahul Dev
RD
Jayant
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL-33199, USA.
Vidya
V
Sagar
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL-33199, USA.
Thangavel
T
Samikkannu
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL-33199, USA.
Adriana
A
Yndart
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL-33199, USA.
Madhavan
M
Nair
D017209:Apoptosis; D020170:Caspase 1 / Q000235:genetics; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; C508585:IL1B protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020170:Caspase 1; D003042:Cocaine