Concordant and discordant interleukin-1–mediated signaling in lung fibroblast Thy-1 subpopulations

JS Hagood, A Mangalwadi, B Guo… - American journal of …, 2002 - atsjournals.org
JS Hagood, A Mangalwadi, B Guo, MW MacEwen, L Salazar, GM Fuller
American journal of respiratory cell and molecular biology, 2002atsjournals.org
Following lung injury or inflammation, fibroblasts mediate either restorative repair or
disordered remodeling. Interleukin (IL)-1 β is a key mediator in the transition from
injury/inflammation to tissue remodeling, in part through its regulation of platelet-derived
growth factor α receptor (PDGF α R). Based on prior demonstration of differential PDGF α R
expression, we hypothesized that subpopulations of fibroblasts would have heterogeneous
responses to IL-1. We report that IL-1 β significantly increases expression of PDGF α R in …
Following lung injury or inflammation, fibroblasts mediate either restorative repair or disordered remodeling. Interleukin (IL)-1 β is a key mediator in the transition from injury/inflammation to tissue remodeling, in part through its regulation of platelet-derived growth factor α receptor (PDGF α R). Based on prior demonstration of differential PDGF α R expression, we hypothesized that subpopulations of fibroblasts would have heterogeneous responses to IL-1. We report that IL-1 β significantly increases expression of PDGF α R in Thy-1 − , but not Thy-1 + fibroblasts. Higher baseline expression of PDGF α R in Thy-1 − fibroblasts is partially abrogated by IL-1 receptor antagonist. There are no differences in IL-1 β binding, as determined by flow cytometry, or in the presence of the type I IL-1 receptor (IL-1RtI) or its associated protein (IL-1RacP) by immunoblotting. IL-1 β induces DNA binding of both nuclear factor κ B (NF- κ B) and CAATT-enhancer binding protein (C/EBP), and activation of p38 mitogen-activated protein kinase in both subpopulations. However, IL-1 β –induced proliferation and expression of IL-6 are significantly higher in Thy-1 − fibroblasts. Heterogeneous responses to IL-1 β despite equivalent presence of both proximal and distal signaling components indicates that parallel signaling pathways are activated selectively in Thy-1 − cells, suggesting a prominent role for this subset in the transition from inflammation to lung remodeling.
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