Induction of human serum amyloid A in Hep 3B cells by IL-6 and IL-1 beta involves both transcriptional and post-transcriptional mechanisms.
Previous studies of murine serum amyloid A (SAA) regulation during inflammatory states or following exposure to macrophage-conditioned medium have raised the possibility that both post-transcriptional and transcriptional mechanisms participate in induction of this family of proteins. Since IL-6 and IL-1 have been shown to induce SAA in human hepatoma cell lines, we explored the possibility that these cytokines might induce human SAA through post-transcriptional as well as transcriptional mechanisms. In kinetic studies, we found that continuous exposure of Hep 3B cells to either IL-6 or IL-1 beta alone caused only minimal increases in SAA mRNA and marginal increases in transcription (as measured by nuclear runon). In contrast, the combination of these cytokines led to a 23-fold increase in transcription, maximal at 12 h, with continuing increase in mRNA, achieving levels more than 1,000-fold greater than baseline by 72 h. This massive disparity between increases in mRNA and in transcription rate strongly supports the participation of post-transcriptional mechanisms in SAA induction by (IL-6 + IL-1 beta), whereas the lag between peaks of transcription and mRNA abundance reflects a relatively slow degradation rate of SAA mRNA. As observed by other workers, mean size of SAA mRNA decreased progressively over the course of incubation. Simultaneous kinetic studies of complement factors B and C3, haptoglobin, and alpha-1 protease inhibitor revealed several different patterns of response to IL-6 and IL-1 beta.
Jiang
S L
SL
Department of Medicine, MetroHealth Medical Center, Cleveland, OH 44109.
Lozanski
G
G
Samols
D
D
Kushner
I
I
D015152:Blotting, Northern; D003176:Complement C3 / Q000096:biosynthesis; D011415:Complement Factor B / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000276:immunology*; D006242:Haptoglobins / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D000685:Serum Amyloid A Protein / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis
D003176:Complement C3; D006242:Haptoglobins; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D000515:alpha 1-Antitrypsin; D011415:Complement Factor B