Interleukin-6 is an Autocrine Growth Factor for Murine Lung Fibroblast Subsets

Interleukin-6 (IL-6) is a pleiotropic cytokine having several functions, including the regulation of immunologic and inflammatory responses. It is produced by many cell types, including lymphocytes, macrophages, and fibroblasts, and is believed to play a major role in pulmonary fibrosis, a condition resulting from expansion of the fibroblast compartment and the accumulation of extracellular matrices secreted primarily by fibroblasts. Production of IL-6 by lung fibroblasts has been well documented; however, it was not known whether all murine lung fibroblasts secreted IL-6 or only subsets thereof. Previous studies in our laboratory have shown that murine lung fibroblasts can be divided into subpopulations based on Thy 1 expression. These subpopulations, Thy 1+ and Thy 1-, differ in morphology, expression of surface markers, and function. IL-6 mRNA was detected in both Thy 1+ and Thy 1- murine fibroblasts and clones using reverse transcriptase polymerase chain reaction (RT-PCR). Interestingly, semi-quantitative RT-PCR and Northern blot analysis demonstrated that IL-6 mRNA was down-regulated in confluent fibroblast cultures versus cultures in log phase growth. Also, IL-6 activity was detected in the supernatants of murine lung fibroblast lines and clones using an IL-6-dependent hybridoma assay. Hybridoma proliferation was inhibited by the addition of a neutralizing anti-mouse IL-6 antibody, indicating that the activity was indeed due to IL-6. The lung fibroblasts expressed IL-6 receptors on their surface as determined by flow cytometry using a rat anti-mouse IL-6 receptor antibody (15A7).(ABSTRACT TRUNCATED AT 250 WORDS)