Ethanol-dependent expression of the NKG2D ligands MICA/B in human cell lines and leukocytes.
Alcohol consumption affects the human immune system, causing a variety of disorders. However, the mechanisms of development of these changes are not fully understood. We hypothesized that ethanol may influence the expression of MICA and MICB, stress-induced molecules capable of regulating the activity of cytotoxic lymphocytes through the interaction with receptor NKG2D, which substantially affects the functionality of cellular immunity. We analyzed the effects of ethanol on MICA/B expression in tumor cell lines and human leukocytes. In the cell line models, ethanol caused different changes in the surface expression of MICA/B; in particular, it induced the translocation of intracellular proteins MICA/B to the cell surface and shedding of MICA (in soluble and microparticle-associated forms) from the plasma membrane. The observed results are not linked with cell death in cultures, taking place only under higher doses of ethanol. Ethanol at physiologically relevant concentrations (and higher) stimulated expression of MICA/B genes in different cell types. The effect of ethanol was more pronounced in hepatocyte line HepG2 compared with hematopoietic cell lines K562, Jurkat, and THP-1. Among the tested leukocytes, the most sensitive to ethanol action were T cells activated ex vivo with IL-2, in which the increase of MICA/B mRNA expression was registered with the smallest dose of ethanol (0.125%). In human monocytes, ethanol may lead to elevations in surface MICA/B levels. Presumably, changes in MICA/B expression caused by ethanol can affect the functions of NKG2D-positive cytotoxic lymphocytes, modulating immune reactions at excessive alcohol consumption.
Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.|Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.
Maria A
MA
Streltsova
Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.|Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.
Anna V
AV
Klinkova
Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.|Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.
Anastasia A
AA
Kuchukova
Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.|Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.
Andrey Y
AY
Kadin
Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.|Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.
Leonid M
LM
Kanevskiy
Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.|Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russian Federation.
Elena I
EI
Kovalenko
D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics* / Q000276:immunology; D009928:Organ Specificity; D061251:Primary Cell Culture; D015398:Signal Transduction
D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D008024:Ligands; C099187:MHC class I-related chain A; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D000431:Ethanol
MICA; MICB; NKG2D; cell stress; ethanol; receptor NKG2D; récepteur; stress cellulaire; éthanol