Regulatory roles of IL-17 and IL-17F in G-CSF production by lung microvascular endothelial cells stimulated with IL-1β and/or TNF-α

The role of the interleukin (IL)-17 family members in the regulation of G-CSF production by lung microvasculature has not been elucidated yet. We therefore investigated the effects of IL-17 and IL-17F on the regulation of G-CSF production by lung microvascular endothelial cells (LMVECs). While a wide range of doses of IL-17 or IL-17F alone did not up-regulate G-CSF production from primary human LMVECs, IL-17 had an enhancing effect on macrophage-derived IL-1β- and TNF-α-induced G-CSF production, whereas IL-17F had an enhancing effect on IL-1β-induced production, but an inhibitory effect on TNF-α-induced secretion. G-CSF production was further enhanced with the combination of three cytokines IL-1β, TNF-α and IL-17. In contrast, three cytokines IL-1β, TNF-α and IL-17F were combined together, G-CSF production was less than that induced by IL-1β or IL-1β plus TNF-α or IL-17F. Moreover, IL-17 plus Th1 or Th2 cytokine had a modest stimulatory effect on TNF-α-induced G-CSF production, whereas IL-17 plus IFN-γ had an inhibitory effect on IL-1β-induced release. Similarly, IL-17F plus IL-10, IL-13 or IFN-γ had an inhibitory effect on IL-1β-induced production. Our findings indicate that CD4 T cell cytokines IL-17 and IL-17F play a differential regulatory role in G-CSF production by LMVECs stimulated with IL-1β and/or TNF-α, which is also sensitive to Th1 and Th2 cytokine modulation.