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Ethanol down‐regulates microglia inflammatory responses augmented by endoplasmic reticulum stress
Author(s) -
Goral Joanna,
Meyer Alice
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.537.4
Subject(s) - unfolded protein response , thapsigargin , xbp1 , endoplasmic reticulum , microglia , chop , chemistry , inflammation , western blot , endocrinology , medicine , nitric oxide , tunicamycin , microbiology and biotechnology , pharmacology , biology , biochemistry , rna , rna splicing , gene
Rationale Endoplasmic reticulum (ER) stress is involved in pathology of neuroinflammatory disorders, multiple sclerosis among them. Ethanol is known to affect immune function, including inflammation. In this study we examined the effect of ER‐stress inducer thapsigargin on inflammatory responses of BV2 mouse microglia. We also examined whether ethanol and inflammatory agents could induce ER stress in BV2 cells. Methods BV2 microglia were stimulated with LPS (100 ng/ml) with or without ethanol (100 mM) for 24 h. The cells were treated with thapsigargin for 2–18 h. The inflammatory response was evaluated by measurement of nitric oxide (NO) production. XBP1 and CHOP, proteins induced by ER stress, were detected by western blot. Results Thapsigargin did not induce, but significantly increased (x 2.5), LPS‐induced NO production by BV2 microglia. This effect was attenuated by ethanol (by 38%). XBP1 and CHOP were detected in BV2 cells exposed to thapsigargin, LPS, and ethanol. Conclusions The presence of XBP1 and CHOP shows that ER stress can be induced in BV2 cells by thapsigargin, LPS and ethanol. LPS‐induced inflammatory responses can be augmented by additional ER stress. However, ethanol – ER stress‐inducing agent itself – can reduce thapsigargin‐augmented inflammatory responses.