Amit Ajay, Kumar Santosh, Dikhit Manas R, Jha Pravin K, Singh Ashish K, Sinha Kislay K, Pandey Krishna, Das V N R, Das Pradeep, Bimal Sanjiva
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.
Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
Cytokine. 2016 Mar;79:38-44. doi: 10.1016/j.cyto.2015.12.016. Epub 2015 Dec 31.
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.
腺苷是一种内源性嘌呤核苷，是一种细胞外信号分子，其在调节内脏利什曼病抗炎细胞因子和免疫致病性中的作用尚未完全明确。在此，我们研究了杜氏利什曼原虫感染与VL患者治疗前后单核细胞上A2B受体表达之间的关系。我们还通过将杜氏利什曼原虫脉冲巨噬细胞暴露于腺苷来研究影响免疫致病性与感染之间相互作用的分子机制。还观察到单核细胞上A2B表达上调与寄生虫负荷增加直接相关。我们的结果还表明，腺苷对IL-10产生的刺激作用和一氧化氮释放的抑制作用严重依赖于A2B受体激活。腺苷对杜氏利什曼原虫诱导的IL-10产生的刺激作用需要ERK1/2激活，且与p-38丝裂原活化蛋白激酶无关。
