IL-17 and IL-17F modulate GM-CSF production by lung microvascular endothelial cells stimulated with IL-1beta and/or TNF-alpha.

In this study, we investigated the roles of CD4 T cell cytokines IL-17 and IL-17F in GM-CSF production from lung microvascular endothelial cells (LMVECs). While a wide range of doses of IL-17 or IL-17F alone did not induce GM-CSF release from LMVECs, IL-17 had an enhancing effect on macrophage-derived IL-1beta- and TNF-alpha-induced GM-CSF mRNA expression and production, whereas IL-17F had an enhancing effect on IL-1beta-induced GM-CSF production, but a marked inhibitory effect on TNF-alpha-induced secretion. GM-CSF production was further enhanced with the combination of three cytokines IL-1beta, TNF-alpha and IL-17 or IL-17F. Additionally, when Th1 or Th2 cytokine was combined with IL-1beta or TNF-alpha, both Th1 and Th2 cytokines had a modest stimulatory effect on TNF-alpha-induced GM-CSF production, whereas IL-4 and IFN-gamma profoundly attenuated IL-1beta-induced secretion. Moreover, the regulation by IL-17 plus Th1 or Th2 cytokine of GM-CSF production from LMVECs treated with IL-1beta or TNF-alpha was dependent on the concentration of IL-17. Our findings indicate that IL-17 and IL-17F play a differential regulatory role in GM-CSF production by LMVECs stimulated with IL-1beta and/or TNF-alpha, which is sensitive to Th1 and Th2 cytokine modulation.