[The effects and mechanisms of interleukin-22 and interferon-γ on epithelial-mesenchymal transition of pleural mesothelial cells].

OBJECTIVE

To investigate the effects of interleukin (IL)-22 and interferon (IFN)-γ on epithelial-mesenchymal transition (EMT) of pleural mesothelial cells, and to explore the relevant signal transduction pathways, in tuberculous pleural effusion.

METHODS

Twenty-two patients (12 males and 10 females, age range 22-64 years, mean 38.4 years) with tuberculous pleurisy hospitalized in department of respiratory medicine of the First People's Hospital of Foshan were recruited from July 2013 to June 2014. Diagnosis was confirmed by pathology. Freshly isolated pleural mesothelial cells (PMCs) from tuberculous pleural effusion were cultured either in medium alone as control, or stimulated with IL-22 and/or IFN-γ, and the phosphorylated signal transducers and activators of transcription (STAT) signalings in PMCs were determined by flowcytometry. In some experiments, STAT inhibitors were added into coculture with IL-22 and/or IFN-γ, and then morphological changes of PMCs were observed, and the expressions of epithelial markers such as cytokeratin-8 and E-cadherin as well as mesenchymal markers such as vimentin and α-Smooth muscle actin (SMA) were also determined by flow cytometry.

RESULTS

As compared with the control group, IFN-γ induced epithelial-mesenchymal transition of PMCs via a STAT1 pathway as evidenced by down-regulation of cytokeratin-8 [(43.8 ± 2.8)% vs (14.3 ± 1.5)%,t=8.1, P<0.05] and E-cadherin [(43.8 ± 1.9)% vs (13.4 ± 1.2)%, t=9.7, P<0.05], and by up-regulation of vimentin [(41.2 ± 2.4)% vs (70.6 ± 3.6)%,t=8.5, P<0.05] and α-SMA [(55.8 ± 2.0)% vs (80.6 ± 2.9)%,t=7.2, P<0.05]. IL-22 not only maintained the epithelial property of PMCs, but also reverted IFN-γ-induced EMT [cytokeratin-8 (62.4 ± 3.1)%, E-cadherin (46.5 ± 3.6)%, vimentin (36.7 ± 2.8)%, and α-SMA (35.2 ± 2.5)% in 'IFN-γ + IL-22' group, all P<0.05 as compared with those of IFN-γ group]. Whereas addition of STAT3 inhibitor significantly abrogated such anti-EMT effect of IL-22 on PMCs [cytokeratin-8 (16.7 ± 0.7)%, E-cadherin (14.4 ± 0.9)%, vimentin (67.9 ± 2.5)%, and α-SMA (79.2 ± 5.7)% in 'IFN-γ + IL-22 + STAT3 inhibitor' group, all P<0.05 as compared with those of 'IFN-γ + IL-22' group].

CONCLUSION

The IL-22-STAT3 signal pathway could revert IFN-γ-induced EMT of PMCs, and might play a protective role in anti-pleural fibrosis in tuberculous pleurisy.