Interleukin‐6 and cyclooxygenase‐2 mediate myofibroblast‐induced polarization of alternatively activated macrophages (734.9)
Bibliographic record
Abstract
Alternatively activated macrophages (AAMΦs) are a macrophage subset induced primarily by the Th2 cytokines IL‐4 and IL‐13. They are associated with anti‐inflammatory functions, such as wound healing and tissue repair and are also protective in animal models of diseases, such as inflammatory bowel disease and multiple sclerosis. In this study we showed that myofibroblasts, also associated with wound healing, may have a putative in vivo role in the induction and maintenance of AAMΦs. Macrophages and myofibroblasts (MFbs) were derived from murine bone marrow and dermal tissue (wild‐type and IL‐6 ‐/‐ ), respectively. MΦ were exposed to IL‐4+IL‐13 conditioned medium (CM) from control MFbs or MFbs treated with a non‐selective cyclooxygenase (COX)‐1 and ‐2 inhibitor (indomethacin) or a selective COX‐1 (SC‐560) or COX‐2 inhibitor (NS‐398). Exposure to control MFb CM enhanced markers of AAMΦ polarization and reduced LPS‐evoked nitric oxide release. These effects were partially reduced using MFbs from IL‐6 ‐/‐ mice, suggesting a role for IL‐6 in this process. CM from indomethacin‐ and NS‐398‐treated MFbs failed to enhance an AAMΦ phenotype ‐ SC‐560 did not have this same effect. Inhibition of EP4 on MΦ also eliminated the effect of MFb CM, implicating PGE 2 . These data indicate a role for IL‐6 and PGE 2 , two molecules commonly linked with pro‐inflammatory functions, in the differentiation of anti‐inflammatory AAMΦs. Grant Funding Source : CCFC, CIHR, CDHF, AIHS
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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) | 0.001 | 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".