Cytokine and insulin regulation of alpha 2 macroglobulin, angiotensinogen, and hsp 70 in primary cultured astrocytes.

Acute-phase proteins and heat shock proteins (hsp) are upregulated following exposure to a number of conditions including bacterial infection, tissue injury, or stress. We show here that alpha 2 macroglobulin (alpha 2M), angiotensinogen (AOG), and hsp 70 are regulated by cytokines in primary cultures of astrocytes. In addition, we have found that insulin modulates the effect of cytokines on these proteins. In cells treated with lipopolysaccharide (LPS) conditioned Raw media, interleukin (IL)-6, or IL-1 beta for 24 h, there was a significant decrease of alpha 2M secretion below control levels. In the absence of insulin, however, similar treatments resulted in a significant increase in alpha 2M secretion. AOG secretion increased significantly following treatment with individual cytokines either in the presence or absence of insulin, but conditioned media did not cause a response in the absence of insulin. Hsp 73 concentrations also increased following treatment with conditioned media and IL-1 beta in the presence or absence of insulin. Following IL-6 treatment, however, hsp levels either decreased (- insulin) or did not change (+ insulin). To determine whether acute-phase proteins are regulated similarly to hsp, astrocytes were subjected to elevated environmental temperatures. Cells incubated at 43 degrees C for 90 min showed a marked increase in AOG secretion. However, alpha 2M and hsp 73 levels remained unchanged. In the absence of insulin, heat shock caused a significant increase of alpha 2M and AOG secretion. Thus, in astrocytes, alpha 2M is upregulated by cytokines and heat shock in the absence of insulin, while in the presence of insulin, cytokines function as negative regulators.(ABSTRACT TRUNCATED AT 250 WORDS)