INDUCTION OF A SUBGROUP OF ACUTE-PHASE PROTEIN GENES IN MOUSE-LIVER BY HYPERTHERMIA

We have demonstrated that two members of the acute phase reactant fami ly of positively regulated genes, alpha(1)-acid glycoprotein (AGP-1 an d AGP-2) and C-reactive protein (CRP) are induced by hyperthermia, whi le two others, the serum amyloid A (SAA) and alpha(1)-antitrypsin (AT) genes, are not. Albumin (ALB), a negative acute phase reactant gene, is also induced by hyperthermia. The AGP-1, AGP-2, and CRP genes requi re glucocorticoids, but not IL-6, IL-1 beta or TNF alpha in response t o hyperthermia. As with LPS, the C/EBP beta mRNA levels increased, whi le the C/EBP alpha mRNA levels decreased in response to LPS. In contra st to the LPS response, C/EBP delta was unchanged. Protein pool levels and DNA-binding activities of the 35 and 20 kDa C/EBP beta isoforms i ncrease, whereas protein pool levels of the 42 kDa C/EBP alpha decreas e and the 30 kDa remained high. These studies suggest that the synthes is of specific C/EBP alpha and C/EBP beta isoforms is induced by hyper thermia, and that the regulation of the AGP-1 and AGP-2 genes during h eat stress may involve one of these isoforms. The difference between t he responses to hyperthermia and LPS is that the former, may not invol ve the participation of cytokines. Furthermore, since cis-acting heat shock elements (HSE) are located in the promoter regions of the ALB, C RP, and C/EBP beta genes, these regulatory sequences may be involved i n the in vivo activation of these genes by hyperthermia. (C) 1998 Else vier Science B.V.