However, even after the drug treatment the colocalization level of WT with EEA1 remained significantly under the level detected in non treated I73T mutant. Furthermore, while hydroxychloroquine did not significantly improve mislocalization defect of the proSP http://www.selleckchem.com/products/AP24534.html CI73T forms, we observed correctional effect of methylprednisolone on localization of proSP CI73T. Namely, methylprednisolone increased localization of the proSP CI73T forms to the syn taxin 2 positive vesicles and decreased their colocalization with EEA1. Nevertheless, even after the pharmacological treatment proSP CI73T never completely acquired WT localization features. Our data suggest the ability of the methylpredni solone drug to partially correct mislocalization defect of proSP CI73T.
Alterations in the intracellular lipid composition and composition of secreted lipids due to expression of SP CI73T and their response to pharmacological treatment The packaging and secretion of lung surfactant lipids is very closely linked to the expression of the hydrophobic surfactant proteins in AECII. Mass spectrometric lipid analysis showed that total phospholipid amount was not changed in transfected MLE 12 cells. However, the phospholipid composition was significantly altered, phosphatidylcholine and sphingomyelin were decreased and lyso phosphatidylcholine and phosphatidylethanolamine were increased in I73T mutant cells. Treatment with methyl prednisolone or hydroxychloroquine did not correct the loss of PC in SP CI73T expressing cells, but it did ame liorate Dacomitinib the LPC increase.
Also significant changes in the pattern of the fatty acids molecular spe PC was reduced with a concomitant increase in LPC, suggesting increased activity of phospholipases. Treat ment with methylprednisolone or hydroxychloroquine corrected to some extent these alterations back toward the WT level. MLE 12 cells expressing SP CI73T secrete soluble factors that stimulate surface expression of CCR2 and CXCR1 on CD4 lymphocytes and CXCR1 on neutrophils Injury of the lung epithelial cell caused by endogenous and exogenous stress may be communicated to the sur rounding immune cells, in particular to the pulmonary cies of different phospholipid classes were measured, sug gesting that the lipid sorting processes of the cells were also affected substantially. The phospholipid secretion by MLE 12 cells was assessed in the supernatant.
Similar as in the intracellu lar lipid pattern, selleck bio PC was decreased by 27% and LPC was increased by 57% in cells expressing SP CI73T, with no changes detected for other phospholipids. Interestingly, the treatment with methylprednisolone or hydroxychloroquine ameliorated the reduction of PC, but had no effect on LPC. Our data suggest that the expression of SP CI73T affected the lipid composition of AECII and alveolar pulmonary sur factant profoundly.
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