Morphine induces the differentiation of T helper cells to Th2 effector cells via the PKC-θ–GATA3 pathway

Background:T help 2 (Th2) cell differentiation by morphine has been verified. However, the underlying mechanism of morphine induces Th2 cell differentiation remains elusive. The aim of the present study was to explore the possible basis of morphine induced Th2 cell differentiation.

Methods:Flow cytometry analysis was used to detect the content of T help 1(Th1) cell and Th2 cell. Enzyme linked immunosorbent assay (ELISA) was performed to determine the levels of IL-4 and IFN-γ. Real-time quantitative polymerase chain reaction, electrophoretic mobility shift assay and Western blotting was conducted in this study.

Results:Th2 cell subset and IL-4 level were elevated in morphine induced naïve T cells. Pathway determining found the protein phosphorylation level of PKC-θ and the expression and activity of the transcription factor GATA3 was also enhanced in the naïve T cells challenged by morphine. Moreover, inhibitor of morphine(naltrexone) or PKC-θ(AEB071) can reverse morphine-induced Th2 cell differentiation.

Conclusion:These results suggested that morphine induce naïve T cell differentiation to Th2 cells via the PKC-θ/GATA3 signal pathway.