A previous study has shown that PCN enhances airway epithelial cell release of IL-8 , a neutrophil chemokine whose production is regulated by oxidant-sensitive transcription factors [50, 51]. Our data indicated that PCN could induce oxidative damage in U937 cells and antioxidant NAC inhibited PCN-induced IL-8 protein expression. In most cases, PCN’s cytotoxicity has been strongly linked
to its potential effects on redox cycle. When entering into cells, PCN oxidizes intracellular pools of NADPH, NADH and GSH directly by accepting electrons, and it passes see more these electrons to oxygen leading to sustained generation of ROS (O2 _ and H2O2) under aerobic condition . Oxidative damage results in unbalance between the oxidant and antioxidant processes. Antioxidant defense system (enzymatic scavengers SOD, CAT and so on and some smal1 molecule antioxidants including NAC, GSH, vitamin C and vitamin E) plays an important role in the elimination of oxygen radical . Cellular GSH levels have
been reported to influence the activity of a BTSA1 datasheet number of transcription factors, including NF-κB, AP-1, and HIF-1α [53, 54]. NAC is a thiol compound that has direct antioxidant properties and also is converted to GSH by cells and thereby limits oxidant-mediated cell injury. By demonstrating the inhibitory effect of NAC on PCN-induced IL-8 production, we indicate that NAC can act as a protective factor that mitigates PCN pro-inflammatory Selleckchem Cilengitide effect on differentiated U937 cells. In short, in this study, we found that PCN could induce PMA-differentiated U937 cells to produce IL-8 by activating MAPKs and NF-κB signaling pathways. Our further studies will focus on understanding the interaction between p38 MAPK, ERK and other cytokine regulators. Knowledge of the mechanisms by which PCN induces PMA-differentiated U937 cells to produce cytokines may provide better understanding and rational approaches for the control of PCN-induced inflammatory processes. Conclusions aminophylline PCN induces U937 cells in a concentration- and time- dependent manner to increase IL-8 mRNA expression and secretion.
Furthermore, MAPKs and NF-κΒ signaling pathways may be involved in the expression of IL-8 in PCN-exposed U937 cells, indicating that the green pus streptozotocin in the P.aeruginosa infection has an important role in inflammation reactions. PCN or TNF-α alone could induce PMA-differentiated U937 cells to express IL-8, but no synergistic effect was observed between these two factors. The mechanism requires further study. Acknowledgments The authors gratefully acknowledge the technical advice and assistance of Dr. HongXin Wang, Dr. RongJian Su, and Mr. ZhiHong Zong. This study was partially funded by the Department of Science and Technology in Liaoning province (No. 201102126) and Liaoning Medical University (No.XZJJ20130105-02). References 1.