Differential expression of interleukin 1α by Thy‐1+ and Thy‐1− lung fibroblast subpopulations: Enhancement of interleukin 1α production by tumor necrosis factor‐α

Abstract

The purpose of this investigation was to determine whether subpopulations of murine lung fibroblasts produced interleukin 1 (IL 1). We previously identified two major populations of pulmonary fibroblasts based on the presence or absence of Thy-1. Thy-1⁺ and Thy-1⁻ subsets synsthesize fibronectin and type I and III collagen, but only the Thy-1⁻ population displays class II major histocompatibility complex antigens after stimulation with interferon-γ and presents antigen to T helper clones. Interestingly, in the current study we determined that only Thy-1⁻ fibroblast lines and clones synthesized IL 1. Although constitutive production was low, tumor necrosis factor -α (TNF-α) stimulated 5-20-fold increases in IL 1 production in Thy-1⁻ fibroblasts. The Thy-1⁺ fibroblasts did not produce IL 1 even after TNF-α treatment. Northern blot analysis of TNF-α treated cells revealed that in the Thy-1⁻ subset increased mRNA levels for IL 1α were detected, while IL 1β mRNA was not detected. Furthermore, IL 1 activity from TNF-α-treated Thy-1⁻ fibroblast membranes and supernatants was completely neutralized by IL 1α-specific antibodies. These observations support the hypothesis that the antigen-presenting Thy-1⁻ subset is important for promoting the inflammation associated with pulmonary fibrosis. In addition, the existence of functional subsets of lung fibroblasts is further substantiated by differential expression of IL 1.