Emerging Roles of Prostaglandins in HIV-1 Transcription
Bibliographic record
Abstract
Prostaglandins (PG), generated by cyclooxygenase (COX), are a group of lipid mediators formed in response to various stimuli. They include PGD 2 , PGE 2 , PGF 2alpha , and PGI 2 . Immediately after synthesis, they are released outside the cell and exert their actions by binding to a G-protein-coupled rhodopsin-type receptor on the surface of target cells. There are seven types of prostaglandin receptors: the PGD receptor, four subtypes of PGE receptor, the PGF receptor, and the PGI receptor. Prostaglandins are involved in host defense against various pathogens. Along with mediating inflammatory symptoms, PGs might suppress some innate immune factors, including nitric oxide (NO) production. These immunomodulatory molecules have been shown to participate in the regulation of virus replication and the modulation of inflammatory responses following infection. Moreover, virus infection also stimulates the expression of a number of proinflammatory gene products, including COX-2, inducible nitric oxide synthase (iNOS) as well as proinflammatory cytokines. An overproduction of PGE 2 (as high as 10 -4 M) is seen in a number of disorders (e.g. allergy, hyper-IgE syndrome, Hodgkin lymphoma, trauma, sepsis, and transplantation), most of which are characterized by elevated Th2 and IgE responses. Elevated levels of PGE 2 have also been reported in individuals infected with HIV-1 and it has been postulated that this may contribute to the immunosuppressive state seen in such virally infected patients. The mechanism(s) responsible for the enhanced prostaglandin formation is still undefined. The initial contact between the virus particle and its target cell might represent the crucial step leading to the production of PGE 2 by macrophages. This concept is supported by the finding that a significant production of endogenous PGE 2 is induced (20-to 40-fold increase) following incubation of primary human monocytes with the HIV-1 external envelope glycoprotein gp120. Given that pro-inflammatory molecules such as PGE 2 are up-regulated during HIV-1 infection, an imbalance in PGJ 2 production is observed in HIV+ individuals. This book chapter will focus on roles of prostaglandins in HIV-1 replication and their potential therapeutic implications. We propose to review mechanisms by which the proinflammatory prostaglandin PGE 2 and the anti-inflammatory prostaglandin PGJ 2 regulate HIV-1 transcription and replication. Specific attention will be placed on how prostaglandins affect the nuclear translocation of NF-B (nuclear factor kappa B), an essential transcription factor for HIV-1 transcription. In addition, signaling pathways as well as other transcription www.intechopen.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".