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Up regulation of A2B adenosine receptor on monocytes are crucially required for immune pathogenicity in Indian patients exposed to Leishmania donovani
Institution:1. Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway;2. Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0316 Oslo, Norway;3. Institute of Cytology, Medical University of Graz, A-8036 Graz, Austria;4. Department of Pathology, University Hospital Essen, Essen, Germany;5. Unit of Pathology, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34151, Italy;1. Winthrop University, Department of Chemistry, Physics and Geology, Rock Hill, SC, 29715, United States of America;2. University of South Carolina, Department of Chemistry and Biochemistry, Columbia, SC 29208, United States of America
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.
Keywords:PBMC  Adenosine  ERK1/2
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