title: Correlation of inducible nitric oxide synthase (iNOS) inhibition with TNF-α, caspase-1, FasL and TLR-3 in pathogenesis of rabies in mouse model.
abstract: The role of inflammatory cytokines such as interleukin-1α/β (IL-1α/β), IL-6, IL-10, tumour necrosis factor-alpha (TNF-α), interferons, nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in pathogenesis of rabies is being actively pursued. Presently, levels of certain immune molecules in pathogenesis of rabies in mice have been investigated. CVS strain of rabies infection resulted in early increase in iNOS, TNF-α, caspase-1, Fas ligand (FasL) and toll-like receptor-3 (TLR-3) mRNA levels in brain, and nitric oxide levels in serum. The severity of clinical signs and microscopic lesions largely correlated with NO levels. Aminoguanidine (AG; iNOS inhibitor) decreased NO production with delay in development of clinical signs and increase in survival time. Prolonged survival time correlated with reduced viral load evident by real-time PCR, reduced fluorescent signals of rabies antigen in brain and reduced immunohistochemistry signals in neuronal cytoplasm. These parameters suggested that nitric oxide did influence the rabies virus replication. Inhibition of iNOS by AG administration led to decreased expression of TNF-α, caspase-1, FasL and TLR-3 mRNA levels suggesting that increase in NO levels in rabies virus infection possibly contributed to development of disease through inflammation, apoptosis and immune-evasive mechanisms.
authors.affiliation: Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
authors.forename: B P
authors.initials: BP
authors.lastname: Madhu
authors.affiliation: Pathology Laboratory, Centre for Animal Disease Research and Diagnosis (CADRAD), ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India. karam.singh@rediffmail.com.
authors.forename: K P
authors.initials: KP
authors.lastname: Singh
authors.affiliation: Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
authors.forename: M
authors.initials: M
authors.lastname: Saminathan
authors.affiliation: Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.affiliation: Division of Animal Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: Wild Animal Disease Diagnostic Laboratory, Institute of Animal Health and Veterinary Biologicals, Bannerghatta Biological Park, Bannerghatta, Bengaluru, Karnataka, India.
authors.forename: V
authors.initials: V
authors.lastname: Manjunatha
authors.affiliation: Department of Pre-Clinical Research, Anthem Biosciences Pvt Ltd, Bommasandra, Bengaluru, Karnataka, India.
authors.forename: C
authors.initials: C
authors.lastname: Harish
authors.affiliation: ICAR-National Institute of Veterinary Epidemiology and Disease Informatics, Bengaluru, Karnataka, India.
authors.forename: G B
authors.initials: GB
authors.lastname: Manjunathareddy
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011818:Rabies / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020170:Caspase 1
keywords: Aminoguanidine; Caspase-1; FasL; Rabies virus; TLR-3; TNF-α