sTREM2 affects cytokine expression profiles in THP‐1 cell model.
Bibliographic record
Abstract
Abstract Background TREM2 is an innate immune receptor expressed on myeloid cells such as microglia and macrophages and is involved in several crucial cellular response pathways including activation and inflammation. TREM2 is cleaved from cell surface by ADAM10/17 releasing as soluble TREM2 (sTREM2) and is reported to be elevated in CSF of AD patients. The relationship between inflammation and sTREM2 remains largely uncharacterized. Method THP‐1 cells were used as a myeloid model. Cells were cultured and treated with different concentrations of human recombinant sTREM2 at 2‐, 4‐, 6‐, and 8‐hour time points. LPS was used as a positive control. RT‐qPCR was used to analyze the expression of several key inflammatory and anti‐inflammatory cytokines. A commercial monoclonal rat anti‐human TREM2 IgG antibody was pre‐incubated with sTREM2 before treatment to assess its ability to mitigate effects of sTREM2 in culture. Result LPS significantly stimulated the expression of TNF‐α, IL‐1β, and IL‐6 as compared to control at all time points, and IL‐10 to a lesser extent. 0.1µg/mL sTREM2 was capable of stimulating the expression of several key pro‐inflammatory cytokines such as TNF‐α, IL‐1β, and IL‐6 post‐treatment. 0.1µg/mL sTREM2 also stimulated the expression of anti‐inflammatory cytokines IL‐10 and CCL17 post treatment. 1.0µg/mL sTREM2 was also capable of stimulating the expression of these cytokines while seemingly affecting the expression of anti‐inflammatory cytokines more consistently. Pre‐incubation of sTREM2 with monoclonal antibody was sufficient at alleviating the expression of TNF‐α, IL‐10 and CCL‐17 induced by exogenous sTREM2. However, the expression of IL‐1β and IL‐6 were amplified following either treatment with antibody alone or sTREM2+antibody. Conclusion Exogenous sTREM2 at a lower concentration (0.1 µg/mL) seems to stimulate expression of several pro‐inflammatory cytokines, while sTREM2 at both a lower (0.1 µg/mL) and a higher concentration (1µg/mL) appear to stimulate the expression of anti‐inflammatory cytokines more consistently in our myeloid cell model. Possibly indicating that different concentrations of sTREM2 may have different effects on cytokine expression profiles in the cell model. Co‐incubation of sTREM2 with a monoclonal anti‐human TREM2 antibody was sufficient to neutralize the effects of sTREM2 on inducing the expression of some cytokines but promoted others.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".