Mesenchymal stem/stromal cells (MSCs) possess some characteristics of immune cells, including a pro-inflammatory phenotype, an immunosuppressive phenotype, antibacterial properties and the expression of Toll-like re...Mesenchymal stem/stromal cells (MSCs) possess some characteristics of immune cells, including a pro-inflammatory phenotype, an immunosuppressive phenotype, antibacterial properties and the expression of Toll-like receptor proteins. Here we show that, similar to immune cells, MSCs retain information from danger signals or environmental stimuli for a period of time. When treated with the pro-inflammatory factors lipopolysaccharide (LPS) or tumor necrosis factor-a (TNF-a), MSCs display increased expression of IL-6, IL-8 and MCP-1. Following re-plating and several rounds of cell division in the absence of stimulating factors, the expression of IL-6, IL-8 and MCP-1 remained higher than in untreated cells for over 7 days. A spike in cytokine secretion occurred when cells were exposed to a second round of stimulation. We primed MSCs with LPS and LPS-primed MSCs had better therapeutic efficacy at promoting skin flap survival in a diabetic rat model than did unprimed MSCs. Finally, we found that several microRNAs, including miR146a, miR150 and miR155, along with the modification of DNA by 5-hydroxymethylcytosine (5hmC), mediate the MSC response to LPS and TNF-e stimulation. Collectively, our data suggest that MSCs have a short-term memory of environmental signals, which may impact their therapeutic potential.展开更多
Ground-level ozone pollution is a menace for vegetation in the northern hemisphere,limiting photosynthetic pigments and suppressing photosynthesis in trees and other types of plants.Phaeophytinization is the process o...Ground-level ozone pollution is a menace for vegetation in the northern hemisphere,limiting photosynthetic pigments and suppressing photosynthesis in trees and other types of plants.Phaeophytinization is the process of converting chlorophylls into phaeophytins,for example by acidifi cation.Ozone is a highly oxidizing molecule and well known to degrade chlorophylls;however,the eff ect of ozone on phaeophytinization in leaves of higher plants is largely unknown.To reveal ozone eff ect on phaeophytinization and evaluate the potential of phaeophytinization as an index of ozone stress in trees,the absorbance at the optical density of 665 nm was measured before(OD_(665))and after(OD_(665a))acidifi cation in three independent experiments with nearly 30 conditions of ozone exposure.Both current ambient and elevated ozone widely aff ected phaeophytinization,as indicated by decreases or increases in the phaeophytinization quotient OD_(665)/OD_(665a).These eff ects were commonly moderate to large in magnitude and practically signifi cant,and occurred even in ozone-asymptomatic leaves.It emerges that the ozone eff ect on phaeophytinization is bimodal,likely depending on the intensity of ozone stress.These results indicate a promising feature of OD_(665)/OD_(665a)as a thorough index of ozone stress in the future,but further studies are needed to reveal the underlying biochemical mechanisms of the bimodal eff ect on phaeophytinization.展开更多
文摘Mesenchymal stem/stromal cells (MSCs) possess some characteristics of immune cells, including a pro-inflammatory phenotype, an immunosuppressive phenotype, antibacterial properties and the expression of Toll-like receptor proteins. Here we show that, similar to immune cells, MSCs retain information from danger signals or environmental stimuli for a period of time. When treated with the pro-inflammatory factors lipopolysaccharide (LPS) or tumor necrosis factor-a (TNF-a), MSCs display increased expression of IL-6, IL-8 and MCP-1. Following re-plating and several rounds of cell division in the absence of stimulating factors, the expression of IL-6, IL-8 and MCP-1 remained higher than in untreated cells for over 7 days. A spike in cytokine secretion occurred when cells were exposed to a second round of stimulation. We primed MSCs with LPS and LPS-primed MSCs had better therapeutic efficacy at promoting skin flap survival in a diabetic rat model than did unprimed MSCs. Finally, we found that several microRNAs, including miR146a, miR150 and miR155, along with the modification of DNA by 5-hydroxymethylcytosine (5hmC), mediate the MSC response to LPS and TNF-e stimulation. Collectively, our data suggest that MSCs have a short-term memory of environmental signals, which may impact their therapeutic potential.
基金partly supported by the National Natural Science Foundation of China (No. 4210070867)the Research grant#201605 of the Forestry and Forest Products Research Institute (FFPRI),JapanKAKENHI grant#JP17F17102 of the Japan Society for the Promotion of Science (JSPS)
文摘Ground-level ozone pollution is a menace for vegetation in the northern hemisphere,limiting photosynthetic pigments and suppressing photosynthesis in trees and other types of plants.Phaeophytinization is the process of converting chlorophylls into phaeophytins,for example by acidifi cation.Ozone is a highly oxidizing molecule and well known to degrade chlorophylls;however,the eff ect of ozone on phaeophytinization in leaves of higher plants is largely unknown.To reveal ozone eff ect on phaeophytinization and evaluate the potential of phaeophytinization as an index of ozone stress in trees,the absorbance at the optical density of 665 nm was measured before(OD_(665))and after(OD_(665a))acidifi cation in three independent experiments with nearly 30 conditions of ozone exposure.Both current ambient and elevated ozone widely aff ected phaeophytinization,as indicated by decreases or increases in the phaeophytinization quotient OD_(665)/OD_(665a).These eff ects were commonly moderate to large in magnitude and practically signifi cant,and occurred even in ozone-asymptomatic leaves.It emerges that the ozone eff ect on phaeophytinization is bimodal,likely depending on the intensity of ozone stress.These results indicate a promising feature of OD_(665)/OD_(665a)as a thorough index of ozone stress in the future,but further studies are needed to reveal the underlying biochemical mechanisms of the bimodal eff ect on phaeophytinization.