Interleukin-17 Regulates the Recruitment of Stromal Progenitor Cells by Increasing Their Responsiveness To Growth Factors under Serum Deprived Growth Conditions

Abstract 833

We have recently found that IL-17 regulated the recruitment of stromal progenitor cells, CFU-STRO, into colony formation under optimal serum growth conditions. In this study we investigated the capacity of IL-17 to induce colony formation under serum deprived conditions. In order to further understand if the mechanism of recruitment involved an increase in responsiveness of stromal progenitor cells to growth factors; stromal progenitor cell were cultured in the presence or absence of IL-17 (50ng/ml) with varying concentrations of serum ranging from 0%, 1%, 2.5% and 10%. In the absence of IL-17, CFU-STRO could not be detected in 0% and 1% serum, however the linear portion of the % serum dose response was between 2.5% and 10% resulting in (M±SEM) 1±.4 and 24±1 CFU-STRO/2.5×10⁵ NC/plate respectively. In contrast, cultures containing IL-17 increased colony formation to detectable levels even in the absence of serum; 0% 1±8:, 1%: 9±.5; 2.5%: 18±1.5, 10%: 27±1. In order to identify the stromal progenitor subtypes being recruited, stromal progenitors were defined as either pure fibroblast, CFU-STROf, or multipotential by giving rise to fibroblasts as well as other cell types including adipocytes, CFU-STROmix. In the 0% serum group, IL-17 induced frequency of both CFU-STROf, 2/5, as well as CFU-STROmix, 3/5. In the 1% serum with IL-17, the frequencies of CFU-STROf were 4/9, and CFU-STROmix was 5/9. In the 2.5% serum group, the frequency distribution of CFU-STROf was 1/5 and CFU-STROmix was 4/5, in contrast with added II-17, frequency of CFU-STROf was 6/18 and CFU-STROmix was 12/18. Both of these subtypes were further characterized by surface area 1-5mm², 6-15mm², 16-30mm², >30mm² (HPP type). Ratios of the average number of colonies for each subtype in control group for CFU-STROf was 1:0:0:0 and CFU-STROmix was 3:1:0:0. In contrast similar cultures containing 2.5% serum with IL-17, ratios of CFU-STROf were 1:4:1:0 and ratios of CFU-STROmix were 2:5:4:1. These data indicate that IL-17 increases both frequency of CFU-STROf and multipotential CFU-STROmix in the absence or presence of suboptimal doses of growth factors by increasing their responsiveness.