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Cellular immunology

ER stress induced impaired TLR signaling and macrophage differentiation of human monocytes.


PMID 23665674

Abstract

Endoplasmic reticulum (ER) stress causes impairment of the intracellular protein synthesis machinery, affecting various organ functions and homeostasis systems, including immunity. We found that ER stress induced by the N-linked glycosylation inhibitor, tunicamycin, caused susceptibility to apoptosis in the human monocytic cell line, THP-1 cells. Importantly, prior to tunicamycin-induced apoptosis, the proinflammatory response to toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS) stimulation was attenuated with respect to the expression of the proinflammatory cytokines. This impaired expression of proinflammatory cytokines was a consequence of the inhibition of NF-κB activation. Moreover, tunicamycin-induced ER stress disturbed the differentiation of THP-1 cells into macrophages induced by phorbol-12-myristate-13-acetate treatment. We also confirmed that ER stress affected the response of primary human monocytes to TLR ligand and their ability to differentiate into macrophages. These data suggest that ER stress imposes an important pathological insult to the immune system, affecting the crucial functions of monocytes.