Mechanisms of suppression of poly I:C-induced activation of NK cells by ethanol.
We have previously reported that ethanol (EtOH) decreases polyinosinic-polycytidylic acid (poly I:C) and interleukin-2 (IL-2)-induced upregulation of natural killer (NK) cell lytic activity in mice. The present study was designed to determine if decreased production of or response to interferon-alpha (IFN-alpha) is involved and if this is associated with inhibited upregulation of perforin or granzyme B. Treatment of mice with poly I:C upregulated IFN-alpha and granzyme B, but not perforin, in the spleen. Administration of EtOH before poly I:C prevented the upregulation of IFN-alpha and granzyme B and decreased perforin levels. EtOH exposure in vivo rendered splenocytes less able to respond to IFN-alpha upon in vitro exposure to poly I:C. Exogenous IFN-alpha only partially prevented this decreased response. Thus, decreased production of and response to IFN-alpha as well as decreased levels of granzyme B and perforin are implicated in the diminished activation of NK cell lytic function in EtOH-treated mice.
Collier
S D
SD
Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Sheveport, LA 71130, USA.
Pruett
S B
SB
D000818:Animals; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D053804:Granzymes; D007369:Interferon Inducers / Q000494:pharmacology*; D016898:Interferon-alpha / Q000187:drug effects / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D054353:Perforin; D011070:Poly I-C / Q000494:pharmacology*; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000097:blood; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D002492:Central Nervous System Depressants; D007369:Interferon Inducers; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D000431:Ethanol; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases; D011070:Poly I-C