Ovocalyxin-36 is an effector protein modulating the production of proinflammatory mediators
Bibliographic record
Abstract
Sepsis is a systemic inflammatory response syndrome during infection. Therapeutic agents are essential to protect the host from sepsis. Ovocalyxin-36 (OCX-36) is a chicken eggshell membrane protein and shares protein sequence and gene organization homology with bactericidal permeability-increasing protein (BPI), lipopolysaccharide-binding protein (LBP) and palate, lung and nasal epithelium clone (PLUNC) proteins that play a major role in innate immune protection. We recently reported that OCX-36 binds to both lipopolysaccharide (LPS) and lipoteichoic acid (LTA) (Cordeiro et al., 2013, PLoS ONE 8, e84112), which is an important activity to neutralize endotoxins and non-endotoxin pyrogens during an inflammatory response. Here we investigated the immune modulating effects of OCX-36 and enzymatically digested OCX-36 (dOCX-36) in vitro and in a mouse model of endotoxemia. OCX-36 alone dose-dependently induced both TNF-α and nitric oxide (NO) production by RAW 264.7 macrophage cells, and this immunostimulatory effect was reduced by enzymatic digestion. In the presence of LPS, dOCX-36 was more effective than intact OCX-36 at reducing LPS-induced secretion of TNF-α from RAW 264.7 cells, but did not reduce NO production. In contrast, OCX-36 increased LPS-induced NO production, both in the presence and absence of FBS, PCR array analysis confirmed that OCX-36 and dOCX-36 differentially regulated genes involved in innate immunity, and dOCX-36 down-regulated the expression of genes involved in LPS signaling and inflammatory responses. In vivo, dOCX-36 was more effective at reducing LPS-induced inflammatory symptoms and inhibiting the local production of pro-inflammatory mediators in the small intestine. These results suggest that OCX-36 and OCX-36 derived peptides may differentially modulate innate immune responses, and support our hypothesis that OCX-36 derived peptides have potential therapeutic applications in sepsis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".