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

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Abstract
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 α2 macroglobulin (α2M), 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‐β for 24 h, there was a significant decrease of α2M secretion below control levels. In the absence of insulin, however, similar treatments resulted in a significant increase in α2M 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‐β 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 43αC for 90 min showed a marked increase in AOG secretion. However, α2M and hsp 73 levels remained unchanged. In the absence of insulin, heat shock caused a significant increase of α2M and AOG secretion. Thus, in astrocytes, α2M is upregulated by cytokines and heat shock in the absence of insulin, while in the presence of insulin, cytokines function as negative regulators. On the other hand, insulin did not modulate the effects of cytokines on the production of AOG in an inverse manner.