Endotoxin-activated cultured neonatal rat cardiomyocytes express functional surface-associated interleukin-1alpha.
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-1alpha and IL-1beta mRNA. The cells expressed functional cell-associated IL-1 activity and a specific anti-IL-1alpha-antibody inhibited the activity. Biologically active IL-1alpha was present at the cell surface of the cardiomyocytes, as indicated in co-culture experiments. Immunohistochemistry showed IL-1alpha-staining of the neonatal cardiomyocytes. Although the cells also expressed IL-1beta mRNA, we did not detect IL-1beta in the supernatants of cultured cardiomyocytes by ELISA or in immunohistochemical staining. Furthermore, neonatal and adult rat heart tissues expressed IL-1alpha mRNA, whereas fetal, but not adult, human cardiac tissues expressed detectable IL-1alpha mRNA. In contrast, IL-1beta mRNA was present in rat and human fetal and adult samples. Furthermore, in patients with dilated or ischemic cardiomyopathy, we measured IL-1beta, but not IL-1alpha, mRNA. These results provide evidence for the presence of functionally active IL-1alpha on the cell surface of neonatal rat cardiomyocytes and may suggest a differential role of IL-1alpha in regulation of cellular functions during development, aging and disease in rat and human heart cells.
Westphal
Elena
E
Martin-Luther-Universität Halle-Wittenberg, Universitätsklinik und Poliklinik für Innere Medizin III, Halle, Germany.
Li Chen
Pilowski
Claudia
C
Koch
Susanne
S
Ebelt
Henning
H
Müller-Werdan
Ursula
U
Werdan
Karl
K
Loppnow
Harald
H
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D004731:Endotoxins / Q000494:pharmacology*; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000196:embryology; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012475:Salmonella
D015415:Biomarkers; D004731:Endotoxins; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D012333:RNA, Messenger