Altered interleukin-1 receptor antagonist and interleukin-18 mRNA expression in myocardial tissues of patients with dilatated cardiomyopathy.
Interleukin-1 (IL-1) is a potent regulator of cell proliferation, inflammation, and contraction of cardiovascular cells. It has been proposed that the IL-1/IL-1ra (IL-1 receptor antagonist) ratio influences these functions. Other members of the IL-1 family and the related caspase-1 also contribute to regulation of IL-1-mediated functions. We determined the mRNA expression of caspase-1, caspase-3, IL-1alpha , IL-1beta , IL-18, IL-1 receptor type I (IL-1-RI), and IL-1ra in left ventricle tissue of hearts from patients with ischemic or dilated cardiomyopathy (ICM or DCM) and in control tissues from unused donor transplant hearts in RT-PCR experiments. We show that the expression of caspase-1, caspase-3, IL-1beta , and IL-1-RI mRNA was not different between patients and control tissues. Furthermore, we did not find detectable amounts of IL-1alpha mRNA in any of these adult myocardial tissues. On the other hand, expression of IL-18 RNA was lower in myocardium of both patient groups compared with control hearts. Furthermore, IL-1ra mRNA expression was significantly lower in tissues of DCM patients compared with ICM patients and controls. This was in line with a trend towards lower IL-1ra protein levels in myocardial tissues of DCM patients. In contrast with the adult tissues discussed above, which did not express IL-1alpha mRNA, commercially available human fetal tissue expressed IL-1alpha mRNA. On the other hand IL-1beta mRNA was present in fetal and in adult human heart tissue. Our data provide evidence for an altered ratio of IL-1/IL-1ra in DCM patients. This dysregulation may contribute to pathogenesis and/or progression of heart disease by modulating the otherwise balanced IL-1-mediated functions in cardiovascular cells.
Westphal
Elena
E
Universitätsklinik und Poliklinik für Innere Medizin III, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.
Rohrbach
Susanne
S
Buerke
Michael
M
Behr
Hagen
H
Darmer
Dorothea
D
Silber
Rolf-Edgar
RE
Werdan
Karl
K
Loppnow
Harald
H
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005333:Fetus; D005786:Gene Expression Regulation; D006321:Heart / Q000196:embryology; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism
D053590:Interleukin 1 Receptor Antagonist Protein; D020382:Interleukin-18; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D012333:RNA, Messenger; D053573:Receptors, Interleukin-1 Type I; D053148:Caspase 3; D020170:Caspase 1