Epithelial interleukin-11. Regulation by cytokines, respiratory syncytial virus, and retinoic acid.

Interleukin-11 (IL-11) is a pleiotropic cytokine with effects that overlap with IL-6. To determine if IL-11 is produced by epithelial cells, we determined whether human alveolar A549 cells and airway 9HTE cells produce IL-11. We also determined whether retinoic acid (RA) altered this IL-11 production. Unstimulated cells produced low levels of IL-11, while IL-1, transforming growth factor (TGF-beta 1), and respiratory syncytial virus (RSV) stimulated IL-11 protein production and mRNA accumulation in a time- and dose-dependent fashion. IL-1 and TGF-beta 1 also interacted in a synergistic, and presumedly transcriptional, fashion since they augmented A549 cell IL-11 protein production and mRNA accumulation without altering IL-11 mRNA half-life. In contrast, IL-4 only weakly stimulated, and IL-7, hepatocyte growth factor, and herpes simplex virus Type 2 did not stimulate, IL-11 production. RA did not alter the IL-11 production of unstimulated or RSV infected cells. It did, however, inhibit rIL-1-stimulated and synergistically augment TGF-beta-stimulated IL-11 production. Thus, IL-1, TGF-beta, and RSV stimulate epithelial-like cell IL-11 production, and RA regulates these inductive processes in a stimulus-specific fashion.