INFLUENCE OF AN INHIBITOR OF JNK ON THE SECRETION OF THE INFLAMMASOME–DEPENDENT PROINFLAMMATORY CYTOKINES

Abstract

Purpose: In this study, we determine the influence of prolonged exposure on organic air pollutants, on the secretion of inflammasome-dependent cytokines IL-1β and IL-18. We also investigate the involvement of the JNK signalling pathway in the inducible IL-1β and IL-18 secretion. Materials and Methods: PBMC from healthy individuals working in an environment with organic particulate matter pollution and healthy donors working in an environment without pollution were isolated by density gradient centrifugation. The isolated cells were stimulated with LPS and C3bgp with or without SP600125, a selective JNK inhibitor and cultured for 6 h. After cell supernatants harvesting, ELISA tests were performed for IL-1β and IL-18 mature protein quantification. Results: The results showed that individuals working in a polluted environment secreted significantly higher levels of the biologically active IL-1β and IL-18 compared to individuals working in a non-polluted environment. We found that SP600125 inhibited the secretion of the mature form of both cytokines in the two groups - individuals with pollution and individuals without pollution significantly. Conclusion: Environmental pollution with organic particulate matter leads to increased IL-1β and IL-18 secretion from peripheral immune cells. JNK transduction pathway is involved in the secretion of the biologically active form of IL-1β and IL-18, after stimulation. We suppose that individuals working in a polluted environment are predisposed to the development of inflammatory or autoimmune/allergic disorders, mediated by the permanent inflammasome activation. The inhibition of the JNK signalling pathway may be beneficial for the treatment of the condition mediated by the increased inflammasome-dependent proinflammatory cytokine secretion.

Keywords

• il-1β
• il-18
• inflammasome
• jnk
• sp600125