Induction of rat α₂‐macroglobulin in vivo and in hepatocyte primary cultures: synergistic action of glucocorticoids and a Kupffer cell‐derived factor

Abstract

Turpentine injection into rats elicits enhanced secretion of acute phase proteins inclucing cr,-macroglobulin (a2M). Hypophysectomized rats, however, do not respond in this way unless dexamethasone is given together with turpentine. On the other hand, dexamethasone injection alone did not result in an induction of cr,M synthesis. When a medium of Kupffer cell cultures was added to hepatocytes, a dose-dependent stimulation of u,M synthesis of up to 4-fold after l&l2 h was observed. However, the presence of low concentrations ( 10m9 M) of dexamethasone was essential for the stimulatory effect. We conclude that the acute phase induction of u,M in hepatocytes requires the synergistic action of glucocorticoids and a non-dialysable factor secreted by Kupffer cells.

Pre-existing inflammatory state compromises heat tolerance in rats exposed to heat stress

“…Survival rate of rats treated with heat exposure only (HE), turpentine combined with heat stress (TϩHE), dexamethasone combined with heat stress (DϩHE) and a combination of turpentine, dexamethasone, and heat stress (TDϩHE). The data were analyzed in categorical scale (died vs. survived) using 2 statistics. The survival rates among the heat-stressed rats are significantly different (P Ͻ 0.05).…”

Murine interleukin 1 stimulates α2‐macroglobulin synthesis in rat hepatocyte primary cultures

“…should be noted that dexamethasone was present in all our hepatocyte primary cultures, since the presence of glucocorticoids is a prerequisite for the synthesis of cu2M as shown in [19]. In the experiments presented a concentration of 1W9 M dexamethasone was used.…”

“…Nevertheless, it remains to be clarified which kind of signal(s) reach(es) the hepatocytes and how the signal(s) finally lead(s) to gene activation. In previous studies with rat hepatocyte primary cultures we found that a2M synthesis can be induced by the simultaneous action of glucocorticoids and a Kupffer cell-derived * To whom correspondence should be addressed factor (hepatocyte stimulating factor, HSF) [18,19]. Up to now the HSF has not been well characterized.…”

Identification of a New Acute Phase Protein

“…Fourth, growth factors such as FGF, insulin, transforming growth factor ␤, and hepatocyte growth factor regulate APPs in a way similar to glucocorticoids. Experimentally, the APR can be induced by injection of animals with inflammatory agents such as turpentine (1,6).…”