Figure 2.
Mice release GDF15 during lung injury induced by Pseudomonas aeruginosa type II secretion system exoproducts. Wild-type (WT) C57Bl/6J mice were intratracheally inoculated with vehicle (n = 6) or the supernatant (SN) of P. aeruginosa grown in culture. Parent P. aeruginosa (P. aeruginosa cell-free SN [PA SN], n = 8) and a genetically modified strain (ΔxcpQ SN, n = 6) deficient for the type II secretion system chaperone protein xcpQ were used. Necropsy was performed 20 hours after inoculation. (A) Gross appearance of BAL fluid, (B) BAL protein concentrations, (C) plasma GDF15 levels (vehicle group, n = 5), and (D) BAL GDF15 levels. (E) Murine lung epithelial cells (MLE12) were exposed in vitro to vehicle or PA SN. Cell lysates were collected 4 hours after exposure, and Gdf15 transcripts (E) and protein (F) were measured. (G) Gdf15fl/fl mice (“control”) or epithelial-specific knockout (KO) Gdf15fl/fl;SFTPC-Cre (“epithelial KO”) mice were exposed to PA SN (n = 9 control and n = 14 epithelial KO), and BAL (G) and plasma (H) GDF15 was measured. In H, plasma GDF15 concentration was normalized to control to compare across experiments. Each tube or point represents an individual mouse, and the group median is displayed. Groups were compared using a Mann-Whitney test.