Mishra K P, Chanda S, Singh S B, Ganju L
Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054, India.
Biometals. 2015 Feb;28(1):175-85. doi: 10.1007/s10534-014-9813-9. Epub 2014 Dec 16.
The hypoxic preconditioning of mammalian cells has been shown to have beneficial effects against hypoxic injuries. However, very little information is available on the comparative analysis of immunological responses to hypoxic and hypoxia mimetic exposure. Therefore, in the present study, mouse peritoneal macrophages and splenocytes were subjected to hypoxia exposure (0.5 % O2) and hypoxia mimetic Cobalt chloride (CoCl2) treatment to evaluate their effect on immune response and delineate the underlying signaling mechanisms. The results obtained indicated that super oxide generation increased while TLR4 expression and cell surface markers like CD25, CD40 and CD69 were suppressed in both the treatments as compared to normoxia. Cobalt chloride treatment increased NF-κB expression, nitric oxide (NO) and iNOS expression, cytokines TNF-α and IL-6 as compared to hypoxia exposure. Our study showed that CoCl2 stabilizes HIF-1α to create hypoxia like conditions but it mainly influences the inflammatory response via NF-κB signaling pathway by skewing the production of proinflammatory molecules like TNF-α, IL-6 and NO.
哺乳动物细胞的低氧预处理已被证明对低氧损伤具有有益作用。然而，关于对低氧和低氧模拟物暴露的免疫反应的比较分析，现有信息非常少。因此，在本研究中，对小鼠腹腔巨噬细胞和脾细胞进行低氧暴露（0.5% O₂）和低氧模拟物氯化钴（CoCl₂）处理，以评估它们对免疫反应的影响，并阐明潜在的信号传导机制。所获得的结果表明，与常氧相比，在两种处理中，超氧化物生成增加，而TLR4表达以及CD25、CD40和CD69等细胞表面标志物受到抑制。与低氧暴露相比，氯化钴处理增加了NF-κB表达、一氧化氮（NO）和诱导型一氧化氮合酶（iNOS）表达、细胞因子TNF-α和IL-6。我们的研究表明，CoCl₂使HIF-1α稳定以创造类似低氧的条件，但它主要通过NF-κB信号通路影响炎症反应，通过改变TNF-α、IL-6和NO等促炎分子的产生。
