scholarly journals Abortive HIV‐1 RNA induces pro‐IL‐1β maturation via protein kinase PKR and inflammasome activation in humans

2021 ◽  
Author(s):  
Melissa Stunnenberg ◽  
John L. Hamme ◽  
Marjolein Trimp ◽  
Sonja I. Gringhuis ◽  
Teunis B.H. Geijtenbeek
Keyword(s):  
Protein Kinase ◽  
Inflammasome Activation ◽  
Hiv 1

HIV-1 gp120 and chemokine activation of Pyk2 and mitogen-activated protein kinases in primary macrophages mediated by calcium-dependent, pertussis toxin–insensitive chemokine receptor signaling

Blood ◽  
2001 ◽  
Vol 98 (10) ◽  
pp. 2909-2916 ◽  
Author(s):  
Manuela Del Corno ◽  
Qing-Hua Liu ◽  
Dominique Schols ◽  
Erik de Clercq ◽  
Sandra Gessani ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Pertussis Toxin ◽  
Chemokine Receptor ◽  
Calcium Release ◽  
Mitogen Activated Protein Kinase ◽  
Macrophage Infection ◽  
Amino Terminal ◽  
Crac Channels ◽  
Mitogen Activated Protein ◽  
Hiv 1

Abstract Human immunodeficiency virus type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry. It was recently demonstrated that HIV-1 glycoprotein 120 (gp120) elevated calcium and activated several ionic signaling responses in primary human macrophages, which are important targets for HIV-1 in vivo. This study shows that chemokine receptor engagement by both CCR5-dependent (R5) and CXCR4-dependent (X4) gp120 led to rapid phosphorylation of the focal adhesion-related tyrosine kinase Pyk2 in macrophages. Pyk2 phosphorylation was also induced by macrophage inflammatory protein-1β (MIP-1β) and stromal cell–derived factor-1α, chemokine ligands for CCR5 and CXCR4. Activation was blocked by EGTA and by a potent blocker of calcium release–activated Ca++(CRAC) channels, but was insensitive to pertussis toxin (PTX), implicating CRAC-mediated extracellular Ca++ influx but not Gαi protein-dependent mechanisms. Coreceptor engagement by gp120 and chemokines also activated 2 members of the mitogen-activated protein kinase (MAPK) superfamily, c-Jun amino-terminal kinase/stress-activated protein kinase and p38 MAPK. Furthermore, gp120-stimulated macrophages secreted the chemokines monocyte chemotactic protein-1 and MIP-1β in a manner that was dependent on MAPK activation. Thus, the gp120 signaling cascade in macrophages includes coreceptor binding, PTX-insensitive signal transduction, ionic signaling including Ca++ influx, and activation of Pyk2 and MAPK pathways, and leads to secretion of inflammatory mediators. HIV-1 Env signaling through these pathways may contribute to dysregulation of uninfected macrophage functions, new target cell recruitment, or modulation of macrophage infection.

Prostaglandin E2 inhibits replication of HIV-1 in macrophages through activation of protein kinase A

2002 ◽  
Vol 215 (1) ◽  
pp. 61-71 ◽  
Author(s):  
Michael M Hayes ◽  
Brian R Lane ◽  
Steven R King ◽  
David M Markovitz ◽  
Michael J Coffey
Keyword(s):  
Protein Kinase ◽  
Prostaglandin E2 ◽  
Protein Kinase A ◽  
Hiv 1 ◽  
Kinase A

scholarly journals The p38 Mitogen-Activated Protein Kinase Critically Regulates Human Keratinocyte Inflammasome Activation

2018 ◽  
Vol 138 (6) ◽  
pp. 1380-1390 ◽  
Author(s):  
Gabriele Fenini ◽  
Serena Grossi ◽  
Samuel Gehrke ◽  
Hans-Dietmar Beer ◽  
Takashi K. Satoh ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Inflammasome Activation ◽  
Human Keratinocyte ◽  
Mitogen Activated Protein

scholarly journals The Potential Role of HIV-1 Vper Interaction with a Protein Kinase VIP4D1 in Vpr-induced Cell Cycle G2 Arrest 911

1998 ◽  
Vol 43 ◽  
pp. 157-157
Author(s):  
Delane Shingadia ◽  
Jian Cao ◽  
Mingzhong Chen ◽  
Chen Wang ◽  
Yuqi Zhao
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Potential Role ◽  
G2 Arrest ◽  
Hiv 1

scholarly journals Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jayakrishna Ambati ◽  
Joseph Magagnoli ◽  
Hannah Leung ◽  
Shao-bin Wang ◽  
Chris A. Andrews ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Hepatitis B ◽  
Prediction Interval ◽  
Inflammasome Activation ◽  
Adjusted Risk ◽  
Innate Immune Signaling ◽  
Diabetes Development ◽  
High Fat Chow ◽  
Prevention Of Diabetes ◽  
Hiv 1

Abstract Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P < 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes.

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