DISTINCT EXPRESSION OF HEAT-SHOCK AND ACUTE-PHASE GENES DURING REGIONAL HEPATIC ISCHEMIA-REPERFUSION

The hepatic response to injury is orchestrated by the expression of di fferent gene groups (i.e., heat shock and acute phase). In the present study, the expression of heat shock. and acute phase genes was analyz ed in the context of a localized injury, regional hepatic ischemia-rep erfusion. Left and median liver lobes were subjected to 1 h of ischemi a, whereas blood flow was maintained to the remainder of the organ. Af ter the period of ischemia, the organ was reperfused, and samples of t he ischemic and nonischemic liver were obtained at different time poin ts during reperfusion. Expression of the heat shock gene, HSP 72, was detected only in the ischemic Liver, whereas expression of the acute p hase gene, beta-fibrinogen, and the interleukin-6-inducible gene, meta llothionein, was maximally induced in the nonischemic liver and attenu ated in the ischemic Liver. To determine how the heat shock and acute phase responses were reprioritized during stress, expression of beta-f ibronogen and HSP 72 was induced simultaneously in the same animal by administration of endotoxin and total body hyperthermia, respectively. Administration of endotoxin did not impede the expression of HSP 72; however, heat shock attenuated, but did not eliminate, the endotoxin-i nduced expression of beta-fibronogen. These observations suggest that the heat shock and acute phase responses are not mutually exclusive.