Polarized macrophage-derived microvesicles differentially modulate intestinal barrier dysfunction and endoplasmic reticulum stress in ulcerative colitis.
- 1Department of Gastroenterology, The First Affiliated Hospital of Shihezi University, Shihezi, 832008, China.
- 2Department of Gastroenterology, The First Affiliated Hospital of Shihezi University, Shihezi, 832008, China. [email protected].
- 3Department of Gastroenterology, The First Affiliated Hospital of Shihezi University, Shihezi, 832008, China. [email protected].
Abstract
Macrophage polarization is critically involved in the initiation and progression of ulcerative colitis (UC); however, whether microvesicles (MVs) released from macrophages with distinct polarization states exert different effects on the intestinal epithelial barrier and endoplasmic reticulum (ER) stress remains unclear. Here, MVs were isolated from M0, M1, and M2 macrophages and evaluated in a dextran sulfate sodium (DSS)-induced mouse colitis model and an inflammatory cytokine-stimulated NCM460 epithelial cell model. M2 macrophage-derived MVs (M2-MVs) mitigated body-weight loss, disease activity, colon shortening, and histopathological injury and partially restored Claudin-1, Occludin, ZO-1, and MUC2 expression. In contrast, M1 macrophage-derived MVs (M1-MVs) tended to aggravate inflammation and barrier disruption. Mechanistically, M2-MVs reduced IL-1β, TNF-α, and IL-6, increased IL-10, and inhibited GRP78, PERK/eIF2α phosphorylation, CHOP, and cleaved caspase-3. Consistent effects were observed in vitro, where M2-MVs restored barrier proteins and reduced ER stress and apoptosis. Moreover, the ER-stress inhibitor 4-phenylbutyric acid attenuated the detrimental effects of M1-MVs, supporting ER stress as an important downstream mechanism. By systematically comparing MVs from M0, M1, and M2 macrophages in parallel, this study reveals a polarization-dependent, bidirectional pattern of macrophage-epithelial communication in experimental colitis and provides preclinical evidence supporting M2-MVs as candidate cell-free effectors for intestinal mucosal repair.
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BibTeX
@article{liang2026polarized,
title = {{Polarized macrophage-derived microvesicles differentially modulate intestinal barrier dysfunction and endoplasmic reticulum stress in ulcerative colitis.}},
author = {Chaoyue Liang and Qasim Khan and Yanling Wei and Sha Wang and Han Wei and Yuyang Jia and Yanqiu Xu and Cuihua Qi},
journal = {Biology direct},
year = {2026},
month = aug,
doi = {10.1186/s13062-026-00923-z},
url = {https://europepmc.org/article/MED/42963556},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Polarized macrophage-derived microvesicles differentially modulate intestinal barrier dysfunction and endoplasmic reticulum stress in ulcerative colitis.
AU - Chaoyue Liang
AU - Qasim Khan
AU - Yanling Wei
AU - Sha Wang
AU - Han Wei
AU - Yuyang Jia
AU - Yanqiu Xu
AU - Cuihua Qi
PY - 2026
DA - 2026/08/03
JO - Biology direct
DO - 10.1186/s13062-026-00923-z
UR - https://europepmc.org/article/MED/42963556
AB - Macrophage polarization is critically involved in the initiation and progression of ulcerative colitis (UC); however, whether microvesicles (MVs) released from macrophages with distinct polarization states exert different effects on the intestinal epithelial barrier and endoplasmic reticulum (ER) stress remains unclear. Here, MVs were isolated from M0, M1, and M2 macrophages and evaluated in a dextran sulfate sodium (DSS)-induced mouse colitis model and an inflammatory cytokine-stimulated NCM460 epithelial cell model. M2 macrophage-derived MVs (M2-MVs) mitigated body-weight loss, disease activity, colon shortening, and histopathological injury and partially restored Claudin-1, Occludin, ZO-1, and MUC2 expression. In contrast, M1 macrophage-derived MVs (M1-MVs) tended to aggravate inflammation and barrier disruption. Mechanistically, M2-MVs reduced IL-1β, TNF-α, and IL-6, increased IL-10, and inhibited GRP78, PERK/eIF2α phosphorylation, CHOP, and cleaved caspase-3. Consistent effects were observed in vitro, where M2-MVs restored barrier proteins and reduced ER stress and apoptosis. Moreover, the ER-stress inhibitor 4-phenylbutyric acid attenuated the detrimental effects of M1-MVs, supporting ER stress as an important downstream mechanism. By systematically comparing MVs from M0, M1, and M2 macrophages in parallel, this study reveals a polarization-dependent, bidirectional pattern of macrophage-epithelial communication in experimental colitis and provides preclinical evidence supporting M2-MVs as candidate cell-free effectors for intestinal mucosal repair.
SN - 1745-6150
ER -