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ER stress differentially affects pro‐inflammatory changes induced by mitochondrial dysfunction in the human monocytic leukemia cell line, THP‐1
Author(s) -
Heo JaeNyoung,
Kim DongYeon,
Lim SuGeun,
Lee Kiboo,
Suk Kyoungho,
Lee WonHa
Publication year - 2019
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11103
Subject(s) - endoplasmic reticulum , thp1 cell line , unfolded protein response , microbiology and biotechnology , cell culture , myeloid leukemia , mitochondrion , hek 293 cells , k562 cells , chemistry , biology , cancer research , genetics
The functional and physical interaction between mitochondria and the endoplasmic reticulum (ER) has been the subject of intense study. To test the effect of this interaction on macrophage inflammatory activation, the human macrophage‐like monocytic leukemia cell line THP‐1 was treated with oligomycin, rotenone, or sodium azide, which induce mitochondrial dysfunction (MD) by blocking the electron transport chain (ETC). MD induced by these agents triggered activation of various sensors and markers of ER stress. This linkage affected macrophage function since LPS‐induced expression of IL‐23 was enhanced by the MD inducers, and this enhancing effect was abolished by inhibition of pancreatic endoplasmic reticulum kinase (PERK) activity. This MD‐mediated ER stress may be universal since it was observed in human embryonic kidney HEK293 cells and colon cancer SW480 cells. On the other hand, MD regulated LPS‐induced activation of the AKT/GSK3β/β‐catenin pathway in a manner not affected by inhibition of PERK or inositol‐requiring enzyme 1α (IRE1α) activities. These results indicate that the occurrence of MD can lead to ER stress and these two events, separately or in combination, can affect various cellular processes.