title: Up regulation of A2B adenosine receptor on monocytes are crucially required for immune pathogenicity in Indian patients exposed to Leishmania donovani.
abstract: Adenosine, an endogenous purine nucleoside is one such extracellular signalling molecule whose role in regulation of anti-inflammatory cytokines and immune pathogenicity in visceral leishmaniasis is not fully understood. Here, we investigated the relationship between Leishmania donovani infection and expression of A2B receptor on monocytes in VL patients in their pre and post treatment stage. We also investigated the molecular mechanisms influencing the interaction between immunopathogenicity and infection by exposing Leishmania donovani pulsed macrophages to Adenosine. A direct correlation of up-regulated A2B expression on monocytes with increased parasite load was also observed. Our results also suggested that A2B receptor activation is critically required for the stimulatory effect of adenosine on IL-10 production and suppression of nitric oxide release. The stimulatory effect of adenosine on Leishmania donovani induced IL-10 production required ERK1/2 activation and is p-38 MAPK independent.
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India; Department of Biotechnology, National Institutes of Pharmaceutical Education and Research, Hajipur 844102, India.
authors.lastname: Vijayamahantesh
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Amit
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India; Department of Biotechnology, National Institutes of Pharmaceutical Education and Research, Hajipur 844102, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India; Department of Bioinformatics, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Manas R
authors.initials: MR
authors.lastname: Dikhit
authors.affiliation: Department of Biotechnology, National Institutes of Pharmaceutical Education and Research, Hajipur 844102, India.
authors.forename: Pravin K
authors.initials: PK
authors.lastname: Jha
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Department of Biotechnology, National Institutes of Pharmaceutical Education and Research, Hajipur 844102, India.
authors.forename: Kislay K
authors.initials: KK
authors.lastname: Sinha
authors.affiliation: Dept. of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Pandey
authors.affiliation: Dept. of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: V N R
authors.initials: VN
authors.lastname: Das
authors.affiliation: Dept. of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Das
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India. Electronic address: drsbimal24@yahoo.com.
authors.forename: Sanjiva
authors.initials: S
authors.lastname: Bimal
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007194:India; D016753:Interleukin-10 / Q000096:biosynthesis; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000096:biosynthesis*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C508609:IL10 protein, human; D043704:Receptor, Adenosine A2B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10; D009569:Nitric Oxide; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000241:Adenosine
keywords: A(2B) receptor; Adenosine; ERK1/2; L. donovani; PBMC