PHENOTYPIC ALTERATIONS OF MACROPHAGE CONTRIBUTES TO EXTRACELLULAR MATRIX DEPOSITION IN CULTURED MACROPHAGE RAW 264.7
Bibliographic record
Abstract
Abstract Macrophages are essential immune cells for the maintenance of tissue homeostasis in the intestinal mucosa barrier. They are also involved in dysregulated process of wound healing, particularly in the context of intestinal damage and tissue repair in inflammatory bowel diseases. Phenotypic plasticity of macrophages from classical M1 to alternative M2 is regulated by a variety of inflammatory cytokines including IFN-γ and IL-4. The IL-4-derived M2 can further differentiate into myofibroblasts. Activated alpha-smooth muscle actin (α-SMA) positive-myofibroblasts are central to the wound healing process and in patients with fibrostenotic Crohn’s disease. They contribute to fibrosis by excessive production of extracellular matrix (ECM) proteins. Despite rapid advances in our understanding of how macrophages help maintain intestinal homeostasis following inflammation, the role of macrophages during the development of intestinal fibrosis in patients with Crohn’s disease is poorly studied. We have previously reported that increased endoplasmic reticulum (ER) stress contributed to the development of TGF-β1-induced intestinal fibrosis. We recently observed that epigallocatechin-3-gallate (EGCG), blocked macrophage polarization from M1 to M2 in bone marrow-derived macrophages from TNBS colitis mice. Here we hypothesized that ER stress regulates the phenotypic change of macrophages and ECM deposition. This notion was examined in RAW 264.7 murine macrophage cells, which were labeled with markers of phenotype: M1-CD38, M2-CD163 after incubation with IFN-γ and IL-4, respectively. Macrophage to myofibroblast transition and evaluation of ECM production were further determined by using myofibroblast marker: α-SMA and ECM markers: collagen 1α1 and periostin. Cells were treated with EGCG to determine whether inhibition of ER stress would block macrophage-to-myofibroblast transition and ECM production. The CD38+M1 increased by 43±2.1% and α-SMA expression increased by 15±1.2% in IFN-γ-induced macrophages compared to untreated control. Correspondingly, collagen 1α1 and periostin also increased by 81± 4.3% and 75±3.7% respectively in CD38+M1. The CD163+M2 increased by 21±1.2% in macrophages treated with IL-4 compared to untreated control. Collagen 1α1 and periostin also increased by 45± 2.3% and 38±1.8% respectively in CD163+M2. ER stress marker, GRP78, increased by 15±0.8% in CD38+ M1 compared to the 5±0.3% increase in CD163+M2. Treatment with EGCG decreased GRP78 by 15±0.8%, collagen 1α1 by 60±3%, and periostin by 63.5±2.1% in CD38+M1 compared to the same markers that decreased by 3±0.2%, 25±1.3%, and 35±1.8% in CD163+M2, respectively. Together, our data suggest that macrophage polarization from M1 to M2 plays a role in macrophage-to-myofibroblast transition, ECM deposition, and increase in ER stress response, which can be blocked by Inhibition of ER stress with EGCG.
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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) | 0.001 | 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".