Trypanosoma cruzi infection induces up-regulation of cardiac muscarinic acetylcholine receptors in vivo and in vitro
| Autor: | C.R. Lankford, Rafael Bonfante-Cabarcas, K. Peraza-Cruces, L. Gutiérrez-Guédez, Claudina Rodríguez-Bonfante, D. Castañeda Perozo |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Chagas disease medicine.medical_specialty Physiology Trypanosoma cruzi Interleukin-1beta Immunology Biophysics Enzyme-Linked Immunosorbent Assay Biology Pharmacology Biochemistry Neurogenic theory Rats Sprague-Dawley Muscarinic acetylcholine receptor Downregulation and upregulation In vivo Internal medicine medicine Animals Myocytes Cardiac General Pharmacology Toxicology and Pharmaceutics lcsh:QH301-705.5 lcsh:R5-920 Immunogenic theory Interleukin-6 General Neuroscience Super-sensitivity Interferon-alpha Cell Biology General Medicine medicine.disease biology.organism_classification Receptors Muscarinic In vitro Rats Up-Regulation Endocrinology lcsh:Biology (General) Chronic Disease Leukocytes Mononuclear lcsh:Medicine (General) |
| Zdroj: | Brazilian Journal of Medical and Biological Research v.41 n.9 2008 Brazilian Journal of Medical and Biological Research Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC Brazilian Journal of Medical and Biological Research, Vol 41, Iss 9, Pp 796-803 (2008) Brazilian Journal of Medical and Biological Research, Volume: 41, Issue: 9, Pages: 796-803, Published: SEP 2008 |
| ISSN: | 0100-879X |
| DOI: | 10.1590/s0100-879x2008000900009 |
| Popis: | The pathogenesis of chagasic cardiomyopathy is not completely understood, but it has been correlated with parasympathetic denervation (neurogenic theory) and inflammatory activity (immunogenic theory) that could affect heart muscarinic acetylcholine receptor (mAChR) expression. In order to further understand whether neurogenic and/or immunogenic alterations are related to changes in mAChR expression, we studied two models of Trypanosoma cruzi infection: 1) in 3-week-old male Sprague Dawley rats chronically infected with T. cruzi and 2) isolated primary cardiomyocytes co-cultured with T. cruzi and peripheral blood mononuclear cells (PBMC). Using [3H]-quinuclidinylbenzilate ([3H]-QNB) binding assays, we evaluated mAChR expression in homogenates from selected cardiac regions, PBMC, and cultured cardiomyocytes. We also determined in vitro protein expression and pro-inflammatory cytokine expression in serum and cell culture medium by ELISA. Our results showed that: 1) mAChR were significantly (P0.05) up-regulated in right ventricular myocardium (means +/- SEM; control: 58.69 +/- 5.54, N = 29; Chagas: 72.29 +/- 5.79 fmol/mg, N = 34) and PBMC (control: 12.88 +/- 2.45, N = 18; Chagas: 20.22 +/- 1.82 fmol/mg, N = 19), as well as in cardiomyocyte transmembranes cultured with either PBMC/T. cruzi co-cultures (control: 24.33 +/- 3.83; Chagas: 43.62 +/- 5.08 fmol/mg, N = 7 for both) or their conditioned medium (control: 37.84 +/- 3.84, N = 4; Chagas: 54.38 +/- 6.28 fmol/mg, N = 20); 2) [(3)H]-leucine uptake was increased in cardiomyocytes co-cultured with PBMC/T. cruzi-conditioned medium (Chagas: 21,030 +/- 2321; control 10,940 +/- 2385 dpm, N = 7 for both; P0.05); 3) plasma IL-6 was increased in chagasic rats, IL-1beta, was increased in both plasma of chagasic rats and in the culture medium, and TNF-alpha level was decreased in the culture medium. In conclusion, our results suggest that cytokines are involved in the up-regulation of mAChR in chronic Chagas disease. |
| Databáze: | OpenAIRE |
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