Regulation and function of newly-recognized IL-1 family cytokines in human bronchial epithelial cells (98.18)

• Published in: The Journal of immunology (1950) Vol. 182; no. 1_Supplement; pp. 98 - 98.18
• Main Authors: Kato, Atsushi, Chustz, Regina T, Schleimer, Robert P
• Format: Journal Article
• Language: English
• Published: 01.04.2009
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.98.18

Abstract The IL-1 family of cytokines, which now includes 11 members, is well known to participate in inflammation. Although the latest IL-1 family cytokines (IL1F5-11) have been shown to be expressed in airway epithelial cells, the regulation of their expression has not been studied. We investigated the regulation of IL1F5-11 in normal human bronchial epithelial cells. Messenger RNAs for IL1F6 and IL1F9, but not IL1F5 or IL1F10, were significantly up-regulated by TNF, IL-1b, IL-17 and TLR3 ligand dsRNA. Messenger RNAs for IL1F7, IL1F8 and IL1F11 (IL-33) were weakly up-regulated by some of the cytokines tested. Notably, mRNAs for IL1F6 and IL1F9 were synergistically enhanced by the combination of TNF/IL-17 or dsRNA/IL-17. IL1F9 protein was detected in the supernatant following stimulation with dsRNA (1.6 ng/ml) or a combination of dsRNA and IL-17 (2.5 ng/ml). IL1F6 protein was detected by western blot. We screened the receptors for IL1F6 and IL1F9 and found that fibroblasts expressed these receptors. We found that IL1F9 activated the MAPKs and the transcription factors including NFkB in primary normal human lung fibroblasts. IL1F9 also stimulated the induction of CXCL8 and CCL20. These results suggest that epithelial activation by respiratory viral infection and exposure to cytokines from Th17 cells (IL-17) may amplify neutrophilic inflammation in the airway via induction of IL1F6 and IL1F9.