Interaction between heat shock and interleukin 6 stimulation in the acute-phase response of human hepatoma (HepG2) cells.
Two characteristic elements of the acute-phase response are an altered pattern of circulating hepatic proteins and fever. Whereas a fever-induced heat shock response could affect expression of acute-phase proteins in the liver, the effects of a modest temperature increase on protein secretion in interleukin-6 (IL-6)-stimulated HepG2 cells were investigated. The response of HepG2 cells to IL-6 stimulation was significantly affected by heat treatment at 40 degreesC. Albumin secretion rates, which were reduced by a factor of 2 in response to either heat shock or IL-6 stimulation alone, were down-regulated by a factor of 4 when IL-6 was administered simultaneously with a continuous 40 degrees C heat shock. IL-6-induced fibrinogen up-regulation was significantly reduced by heat treatment (P < .01), and secretion rates were indistinguishable from control levels after 2 days (P > .10). Unexpectedly, heat shock at 40 degrees C induced a fivefold up-regulation of haptoglobin production in the absence of IL-6. Simultaneous heat shock and IL-6 stimulation caused a synergistic enhancement of haptoglobin expression, with secretion rates increasing up to 30-fold compared with unstimulated control cells. For all three proteins, the interaction between temperature and IL-6 concentration was statistically significant (P < .001). Heat treatment resulted in significant alterations of both the kinetics and sensitivity of IL-6-induced protein synthesis, suggesting a major modification of the mechanism of acute-phase protein regulation at 40 degreesC. In summary, the data show that heat shock can significantly modulate the pattern of acute-phase protein expression and that fever may be an important regulatory factor in the acute-phase response.
Department of Mechanical Engineering, University of Illinois, Chicago, IL, USA.
J O
JO
Karlsson
M L
ML
Yarmush
M
M
Toner
D000209:Acute-Phase Proteins / Q000096:biosynthesis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular; D005340:Fibrinogen / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006242:Haptoglobins / Q000096:biosynthesis / Q000235:genetics; D006358:Hot Temperature; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D008113:Liver Neoplasms; D012709:Serum Albumin / Q000096:biosynthesis; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D006242:Haptoglobins; D015850:Interleukin-6; D012709:Serum Albumin; D005340:Fibrinogen