Amyloid-β peptide-induced extracellular S100A9 depletion is associated with decrease of antimicrobial peptide activity in human THP-1 monocytes
Bibliographic record
Abstract
BACKGROUND: S100A9 protein (myeloid-related protein MRP14, also referred to as calgranulin B) is a reliable marker of inflammation, an important proinflammatory factor of innate immunity and acts as an additional antimicrobial peptide in the innate immune system. Evidence indicates that S100A9 contributes to Alzheimer's disease (AD) pathology, although the precise mechanisms are not clear. METHODS: We were interested to study the mechanisms of S100A9 release upon Aβ1-42 stimulation, the potential roles of extracellular S100A9 depletion in Aβ-induced cytotoxicity, and the interaction with innate immune response in THP-1 monocytic cells that have been challenged with mostly Aβ1-42 monomers instead of oligomers. We used protein preparation, Ca(2+) influx fluorescence imaging, MTT assay, siRNA knockdown, colony forming units (CFUs) assay and western blotting techniques to perform our study. RESULTS: Aβ1-42 monomers elicited a marked decrease of S100A9 release into the cell culture supernatant in a dose-dependent manner in human THP-1 monocytes. This reduction of S100A9 release was accompanied by an increase of intracellular Ca(2+) level. Aβ1-42-mediated decrease of S100A9 release was not associated with Aβ1-42-induced cytotoxicity as measured by MTT reduction assay. This observation was confirmed with the recombinant S100A9, which had little effect on Aβ1-42-induced cytotoxicity. Moreover, depletion of S100A9 with siRNA did not significantly evoke the cell toxicity. On the other hand, Aβ1-42-induced extracellular S100A9 depletion resulted in decreased antimicrobial activity of the culture supernatant after Aβ1-42 stimulation. Immunodepletion of S100A9 with anti-S100A9 also decreased the antimicrobial peptide activity of the vehicle treated culture supernatant. Consistently, the recombinant S100A9 clearly elicited the antimicrobial peptide activity in vitro, confirming the observed antimicrobial activity of S100A9 in the culture supernatant. CONCLUSION: Collectively, our findings suggest that the mostly monomeric form of Aβ1-42 negatively regulates the innate immune system by down-regulating the secretion of S100A9, which is likely a main mediator of antimicrobial activity in the conditioned media of human THP-1 monocytes.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 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) | 0.000 | 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".