title: Microarray analysis of the mammalian thromboxane receptor-Trypanosoma cruzi interaction.
abstract: Trypanosoma cruzi, the etiological agent of Chagas disease, causes vasculopathy and cardiomyopathy in humans and is associated with elevated levels of several vasoactive molecules such as nitric oxide, endothelin-1 and thromboxane A 2 (TXA 2). Parasite derived TXA 2 modulates vasculopathy and other pathophysiological features of Chagasic cardiomyopathy. Previously, we demonstrated that in response to infection with T. cruzi, TXA 2 receptor (TP) null mice displayed increased parasitemia; mortality and cardiac pathology compared with wild type (WT) and TXA 2 synthase null mice. In order to further study the role of TXA 2-TP signaling in the development of Chagas disease, GeneChip microarrays were used to detect transcriptome changes in rat fat pad endothelial cells (RFP-ECs) which is incapable of TXA 2 signaling (TP null) to that of control (wild type) and RFP-EC with reconstituted TP expression. Genes that were significantly regulated due to infection were identified using a time course of 2, 18 and 48 hrs post infection. We identified several key genes such as suppressor of cytokine signaling (SOCS-5), several cytokines (CSF-1, CXCF ligands), and MAP kinases (MAPK-1, Janus kinase) that were upregulated in the absence of TP signaling. These data underscore the importance of the interaction of the parasite with mammalian TP and may explain the increased mortality and cardiovascular pathology observed in infected TP null mice.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY USA. herbert.tanowitz@einstein.yu.edu
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Tanowitz
authors.forename: Aparna
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Ashton
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Fabiana S
authors.initials: FS
authors.lastname: Machado
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiss
authors.forename: Shankar
authors.initials: S
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D006790:Host-Parasite Interactions; D015151:Immunoblotting; D051379:Mice; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017482:Receptors, Thromboxane / Q000235:genetics / Q000378:metabolism*; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism*; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017482:Receptors, Thromboxane; D050826:Suppressor of Cytokine Signaling Proteins; D013928:Thromboxane A2; D020928:Mitogen-Activated Protein Kinases