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

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.