Overexpression of cardiotrophin-1 and gp130 during experimental acute Chagasic cardiomyopathy.
Cardiotrophin-1 (CT-1), a cytokine with structural similarities to interleukin-6, has been shown to signal through gp130-dependent pathways. In vitro, CT-1 promotes the survival and induces hypertrophy of neonatal cardiomyocytes. Since acute Chagas' disease involves an inflammatory response followed by chamber dilation, with subsequent compensatory hypertrophy, we hypothesized CT-1 and gp130 may participate in this disease process. Thus, we investigated expression and localization of these moieties during acute Chagasic cardiomyopathy. Lewis rats (n = 6/group) were either inoculated with cell culture-derived T. cruzi trypomastigotes or saline, and sacrificed 15 days later. Hearts were collected for histology, immunohistochemistry (IHC), mRNA, and protein analyses. Histology showed dense myocardial infection with amastigotes and diffuse mononuclear cell infiltrate. Northern blot analysis showed low level expression of CT-1 mRNA in controls, which was markedly elevated in infected animals (2.5-fold; P < 0.001). Similarly, Western blotting showed a twofold elevation of CT-1 protein in infected animals (P < 0.025). Likewise, levels of both gp130 mRNA and protein were low in controls, but were approximately threefold higher in infected animals. IHC showed weak and diffuse staining for CT-1 in control myocardium, while intense staining especially localized to the cytoplasmic region of cardiomyocytes, was found in infected animals. Although gp130 immunoreactivity was observed in both normal and infected myocardium, more intense staining was found in infected animals. Unlike CT-1, gp130 staining was granular, and was present in both the cytoplasm as well as in the perinuclear region. These data suggest that there is substantial overexpression of both CT-1 and gp130 in the heart during acute Chagasic carditis. Their overexpression may provide a mechanism for myocyte protection, and for development of compensatory cardiac hypertrophy following myocardial damage in this form of cardiomyopathy.
Chandrasekar
B
B
Department of Medicine/Cardiology, The University of Texas Health Science Center, San Antonio 78284-7872, USA.
Melby
P C
PC
Pennica
D
D
Freeman
G L
GL
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D015153:Blotting, Western; D002598:Chagas Cardiomyopathy / Q000378:metabolism* / Q000473:pathology; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D012333:RNA, Messenger; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction; D014349:Trypanosoma cruzi / Q000502:physiology*
D015703:Antigens, CD; D016207:Cytokines; C494200:Il6st protein, mouse; C494201:Il6st protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D050822:Cytokine Receptor gp130; C092073:cardiotrophin 1