title: Splenocyte apoptosis in Plasmodium berghei ANKA infection: possible role of TNF-α and TGF-β.
abstract: Cerebral malaria is associated with the circulating levels of tumour necrosis factor alpha (TNF-α) and transforming growth factor β (TGF-β), but association between these two cytokines and implications in splenocyte apoptosis remain largely obscured. We have evaluated the outcome of TGF-β and TNF-α production in the context of splenocyte apoptosis during Plasmodium berghei ANKA (PbA) infection. Blood-stage PbA infection confirmed blood-brain barrier disruption, disarray of white pulp, increase in percentage of sub-G0/G1 and splenocyte apoptosis. Flow cytometric analysis reveals up-regulation of Fas-L followed by caspase-8 and caspase-3 activation and signifies possible involvement of Fas-L-mediated splenocyte apoptosis. We have observed down-regulation of TGF-β and up-regulation of TNF-α in tissue and serum level, respectively, during PbA infection. Association between the production of TGF-β and the severity of malaria infection in splenocytes was verified with TGF-β inhibitor that exacerbated the apoptotic process. In contrary, TNF-α inhibitor causes significant delay in apoptotic process, but could not alter the lethality of parasite. Thus, results from this study suggest that the critical balance between TGF-β and TNF-α might have a key role on Fas-L-mediated splenocyte apoptosis during experimental cerebral malaria.
authors.affiliation: Immunology Lab, Department of Zoology, University of Calcutta, Kolkata, India.
authors.forename: T
authors.initials: T
authors.lastname: Keswani
authors.forename: A
authors.initials: A
authors.lastname: Bhattacharyya
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001549:Benzamides / Q000494:pharmacology; D002470:Cell Survival / Q000276:immunology; D004149:Dioxoles / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000276:immunology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006651:Histocytochemistry; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000276:immunology; D051379:Mice; D018512:Parasitemia / Q000276:immunology; D010431:Pentoxifylline / Q000494:pharmacology; D010962:Plasmodium berghei / Q000276:immunology*; D013154:Spleen / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D053222:Fas Ligand Protein; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline