Background: IL-17 is a critical proinflammatory cytokine in Collagen Induced Arthritis (CIA) and lung host defense. Follistatin-like protein-1 (FSTL-1), a proinflammatory glycoprotein mediates the development of CIA. FSTL-1 mediates IL-17-dependent stimulation of IL-6 by an unknown mechanism. Methods: ST2 cells with shRNA for FSTL-1 (shFSTL-1) and control (shCntrl) sequences were stimulated with 8ng/mL IL-17 and 2ng/mL TNFα. Transcript abundance was assessed by qRT-PCR. Protein secretion was assessed by Luminex. IL-17 receptor surface expression was assessed by FACS analysis. Results: Compared to shCntrl cells, shFSTL-1 cells had 1)decreased transcripts of IL-6 (275±3 vs. 43±3), G-CSF (1802±7 vs. 1325±93), IL-17RA (0.798±0.02 vs. 0.504±0.03) and IL-17RC (1.28±0.01vs. 0.72±0.1) relative to unstimulated cells, 2)decreased protein secretion IL-6 (25142 ± 229pg/ml vs. 2542 ± 37), G-CSF (388 ± 32 pg/ml vs. 27.8 ± 3.9 ) secretion, and 3)decreased IL-17RA surface expression when unstimulated (86.6% vs. 44.8%) or stimulated with ligand (14.1% vs. 5.2%) despite similar IL-17RC surface expression when unstimulated (93.6% vs. 91.3%) or stimulated (59.2% vs. 49.5%). Conclusions: FSTL-1 mediates IL-17 stimulated IL-6 and G-CSF production in ST2 cells. FSTL-1 influences transcript abundance of IL-17RA and IL-17RC, but shFSTL-1 attenuates surface expression of IL-17RA alone, suggesting that FSTL-1 regulates IL-17 signalling by influencing the cell surface expression of IL-17RA.
- Copyright © 2013 by The American Association of Immunologists, Inc.