Macrophage tolerance response to <i>Aggregatibacter actinomycetemcomitans</i> lipopolysaccharide induces differential regulation of tumor necrosis factor‐α, interleukin‐1β and matrix metalloproteinase 9 secretion
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Bibliographic record
Abstract
BACKGROUND AND OBJECTIVE: The lipopolysaccharide of Aggregatibacter actinomycetemcomitans, a potent stimulator of the immune system, induces the secretion of inflammatory mediators that modulate periodontal tissue destruction. In this study, we investigated the tolerance response of human macrophages to stimulation with A. actinomycetemcomitans lipopolysaccharide. MATERIAL AND METHODS: U937 monocytes were differentiated into adherent macrophage-like cells by treatment with phorbol myristic acid. Macrophage-like cells were then pretreated for 24 h with either 0.01 or 0.1 microg/mL LPS A. actinomycetemcomitans. Culture medium supernatants were removed and cells were restimulated with LPS at 1 microg/mL. Cell-free supernatants were collected after 24 h of stimulation and analyzed by ELISA for TNF-alpha, IL-1 beta, IL-6, IL-8, PGE(2) and MMP-9. RESULTS: Phorbol myristic acid-differentiated U937 macrophages treated with low doses of lipopolysaccharide developed tolerance to subsequent lipopolysaccharide treatments, resulting in significantly reduced secretion of tumor necrosis factor-alpha. However, this tolerance response was associated with increased secretion of interleukin-1 beta and matrix metalloproteinase 9, whereas the secretion of interleukin-6, interleukin-8 and prostaglandin E(2) was unaffected. Phosphatidylinositol-3'-kinase inhibitors added during the tolerance-induction period markedly attenuated the increase in interleukin-1 beta secretion but had no effect on tumor necrosis factor-alpha. CONCLUSION: This study showed that A. actinomycetemcomitans lipopolysaccharide can induce a tolerance response in macrophages that alters the secretion of two important inflammatory mediators as well as of the tissue-degrading enzyme matrix metalloproteinase-9. This phenomenon may play a role in modulating the host inflammatory response and the progression of periodontitis.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 it