Down-regulation of protein kinase C in murine splenocytes: a potential mechanism for 2-acetylaminofluorene-mediated immunosuppression.
2-Acetylaminofluorene (AAF), an arylamide carcinogen, inhibited in a dose dependent manner mouse spleen cell proliferation in response to lipopolysaccharide (LPS). The objective of the present studies was to investigate the effects of AAF on protein kinase C (PKC) activation, an enzyme required for LPS-induced splenocytes proliferation. After treatment with 50 microM AAF for 18 h, PKC activity in the cytosolic fraction decreases by 50% from the control level, and splenocytes lost 30% of total PKC activity. Furthermore, as determined by the electrophoretic mobility shift assay, AAF inhibited the binding activity of the transcription factor complex, NF-KB, whose LPS-mediated induction is dependent on PKC activation in murine splenocytes. These results strongly suggest that LPS-mediated signaling in spleen cells is interrupted by AAF early in the signal transduction pathway, at a point proximal to the activation of PKC.
Lee
M
M
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Kuson-dong Yusong-gu Taejon, Korea.
Kim
H M
HM
Yang
K H
KH
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015342:DNA Probes / Q000737:chemistry; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007165:Immunosuppression Therapy; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013154:Spleen / Q000166:cytology* / Q000201:enzymology
D002273:Carcinogens; D015342:DNA Probes; D008070:Lipopolysaccharides; D015073:2-Acetylaminofluorene; D011493:Protein Kinase C