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.
Elias
J A
JA
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Zheng
T
T
Einarsson
O
O
Landry
M
M
Trow
T
T
Rebert
N
N
Panuska
J
J
D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D017370:Interleukin-11 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology*
D016207:Cytokines; D017370:Interleukin-11; D012333:RNA, Messenger; D014212:Tretinoin