Induction of a subgroup of acute phase protein genes in mouse liver by hyperthermia

Abstract

We have demonstrated that two members of the acute phase reactant family of positively regulated genes, α 1-acid glycoprotein (AGP-1 and AGP-2) and C-reactive protein (CRP) are induced by hyperthermia, while two others, the serum amyloid A (SAA) and α 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 require glucocorticoids, but not IL-6, IL-1β or TNFα in response to hyperthermia. As with LPS, the C/EBPβ mRNA levels increased, while the C/EBPα mRNA levels decreased in response to LPS. In contrast to the LPS response, C/EBPδ was unchanged. Protein pool levels and DNA-binding activities of the 35 and 20 kDa C/EBPβ isoforms increase, whereas protein pool levels of the 42 kDa C/EBPα decrease and the 30 kDa remained high. These studies suggest that the synthesis of specific C/EBPα and C/EBPβ isoforms is induced by hyperthermia, and that the regulation of the AGP-1 and AGP-2 genes during heat stress may involve one of these isoforms. The difference between the responses to hyperthermia and LPS is that the former, may not involve the participation of cytokines. Furthermore, since cis-acting heat shock elements (HSE) are located in the promoter regions of the ALB, CRP, and C/EBPβ genes, these regulatory sequences may be involved in the in vivo activation of these genes by hyperthermia.