Increased expression of interleukin-1beta and its novel splice variant in canine hearts with volume overload.
Volume overload frequently caused in dogs by chronic degenerative valvular disease (CDVD), eventually leads to cardiac failure. Experimental and clinical evidences demonstrate that increased interleukin-1beta serum level in patients with heart insufficiency correlates with the severity of failure irrespective of its etiology. Very little is known about the IL-1beta expression in failing vs. non-failing myocardium. IL-1beta transcript level was determined in the CDVD dogs (n=17) and control animals (n=9) without cardiac insufficiency by real-time PCR. IL-1beta transcript level in failing hearts was higher than in the control. In both groups the highest IL-1beta level was detected in the left ventricles. Although IL-1beta is a major pro-inflammatory cytokine most of the CDVD dogs displayed no inflammatory infiltrates into the myocardium. Massive fibrosis was observed in the control group, unlike the failing hearts, in which cardiomyocyte hypertrophy and atrophy dominated. The alternative IL-1beta transcript identified here (IL-1betasv1) was significantly elevated in the failing myocardium compared with the control group. Increased IL-1beta expression seems to be associated with mechanical heart overload. Its endogenous origin, and certain histopathological findings attributed to IL-1beta indicate its importance in cardiac hypertrophy and failure. The lack of some typical IL-1beta actions, i.e. inflammatory, pyrogenic and fibrotic, may suggest a different role of this cytokine in myocardium. It appears that the canine IL-1beta gene can be transcribed in two ways in heart tissue, with the IL-1betasv1 form present mainly in failing hearts.
Kiczak
Liliana
L
Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Norwida 31, 50-375 Wroclaw, Poland. liliana.kiczak@up.wroc.pl
Paslawska
Urszula
U
Bania
Jacek
J
Ugorski
Maciej
M
Sambor
Izabela
I
Kochman
Agata
A
Blach
Joanna
J
Chelmonska-Soyta
Anna
A
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001344:Autopsy; D001831:Body Temperature; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006349:Heart Valve Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D012333:RNA, Messenger