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Endoplasmic reticulum stress contributes to ferritin molecules‐mediated macrophage migration via P‐selectin glycoprotein ligand‐1
Author(s) -
Wang ChiMei,
Chen YueHwa,
Lee YuChieh,
Chang JungSu
Publication year - 2017
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201600458
Subject(s) - ferritin , endoplasmic reticulum , unfolded protein response , macrophage , inflammation , chemistry , tumor necrosis factor alpha , endocrinology , medicine , immunology , microbiology and biotechnology , biology , biochemistry , in vitro
Scope Obesity is associated with elevated serum ferritin and increased macrophage activation and infiltration; however, the causal mechanisms underlying this relationship remain undefined. Methods and results Serum ferritin and soluble P‐selectin glycoprotein ligand (sPSGL)‐1 level were higher in obese adolescents and patients with moderate nonalcoholic fatty liver disease (NAFLD) compared with controls (all p < 0.05). Multivariate linear regression revealed that serum ferritin was independently associated with sPSGL‐1 ( B = 0.249, 95% confidence interval: 0.011–0.487, p = 0.041) after adjustment for covariates. The messenger (m) RNA expression of GRP78/Bip, ferritin, and PSGL‐1 in leukocytes was greater in patients with nonalcoholic fatty liver disease than in controls. An animal study showed that a tunicamycin injection (an endoplasmic reticulum stress inducer) triggered serum sPSGL‐1 and ferritin elevation (all p < 0.01). An in vitro study revealed that serum ferritin and apoferritin induced tumor necrosis factor‐α and sPSGL‐1 secretion (all p < 0.01). A wound healing assay showed that PSGL‐1 blocking inhibited apoferritin‐mediated macrophage migration. GRP78/Bip knockdown by the endotoxin EGF‐SubA completely inhibited apoferritin‐mediated macrophage migration and PSGL‐1 expression at the protein and mRNA levels (all p < 0.05). Conclusion ER stress associated mechanisms are required for apoferritin‐/ferritin‐mediated macrophage migration via the PSGL‐1‐dependent pathway.