Human lung endothelial cells produce IL-33 and TSLP simultaneously after dsRNA stimulation
Monday, March 5, 2018: 2:15 PM
S230AB (Convention Center)
Maiko Emi-Sugie, PhD, , , , , ,
RATIONALE: Asthma is characterized by type 2 inflammation, in which IL-33 and TSLP play critical roles upon viral infection. Recent studies revealed that not only epithelial cells, but also other tissue cells, can release these two cytokines. Moreover, IL-33 and TSLP showed the same kinetics of induction in rhinovirus-infected mice, suggesting that the existence of cells that concurrently produce IL-33 and TSLP, even though IL-33 is reportedly released by cell damage whereas TSLP is not. In this study, we screened for airway structural cells that simultaneously produced IL-33 and TSLP upon exposure to polyI:C, an analog of viral dsRNA.

METHODS: Normal human lung microvascular endothelial cells (HMVEC-L) and Normal human lung fibroblasts (NHLF), Normal human bronchial epithelial cells (NHBE) and Normal human bronchial smooth muscle cells (BSMC) were stimulated with 1 μg/ml polyI:C. mRNA expression and protein concentrations were determined by qPCR and ELISA, respectively.

RESULTS: Only HMVEC-L showed simultaneous IL-33 and TSLP mRNA/protein up-regulation at 36 h after polyI:C exposure, while NHBE, NHLF and NHBE did not. HMVEC-L derived from each of 7 different donors showed up-regulation of these cytokines. Among several tested TLR ligands, only polyI:C induced expression of these cytokines, and the induction was specific to lung-derived endothelial cells, but not dermal-, umbilical vein- or coronary artery-derived endothelial cells.

CONCLUSIONS: Respiratory virus-induced type 2 inflammation is likely to be mediated at least in part by simultaneous release of IL-33 and TSLP by lung endothelial cells. The molecular mechanisms of such cytokine release warrant further study.