Endotoxin-activated cultured neonatal rat cardiomyocytes express functional surface-associated interleukin-1α

Abstract

Interleukin-1 (IL-1) is a potent regulator of cardiovascular proliferation, apoptosis, contraction or production of inflammatory mediators. Thus, we investigated expression and function of IL-1 in cultured neonatal rat heart cells upon endotoxin stimulation. We show that cultured neonatal rat cardiomyocytes expressed IL—1α and IL—1β mRNA. The cells expressed functional cell-associated IL—1 activity and a specific anti-IL—1α-antibody inhibited the activity. Biologically active IL—1α was present at the cell surface of the cardiomyocytes, as indicated in co-culture experiments. Immunohistochemistry showed IL—1α-staining of the neonatal cardiomyocytes. Although the cells also expressed IL—1β mRNA, we did not detect IL—1β in the supernatants of cultured cardiomyocytes by ELISA or in immunohistochemical staining. Furthermore, neonatal and adult rat heart tissues expressed IL—1α mRNA, whereas fetal, but not adult, human cardiac tissues expressed detectable IL—1α mRNA. In contrast, IL-1β mRNA was present in rat and human fetal and adult samples. Furthermore, in patients with dilated or ischemic cardiomyopathy, we measured IL—1β, but not IL—1α, mRNA. These results provide evidence for the presence of functionally active IL—1α on the cell surface of neonatal rat cardiomyocytes and may suggest a differential role of IL—1α in regulation of cellular functions during development, aging and disease in rat and human heart cells.