Host: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
Name : WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
Location : Kyoto
Date : July 01, 2018 - July 06, 2018
YKL-40, also called chitinase-3-like-1 protein, is found to be increased in the sputum and serum of patients with asthma, in whom YKL-40 levels in both compartments correlate with the severity of asthma. Although YKL-40 is secreted by epithelial cells, macrophages and neutrophils in the airway inflammation and remodeling in asthma, the pathogenic function of YKL-40 remains unclear. To explore whether YKL-40 is a therapeutic target for asthma, this study examined the role of YKL-40 in bronchial epithelial cells (Beas-2B). We found that stable suppression of YKL-40 expression by siRNA increased IL-33 mRNA levels by around 10-fold in Beas-2B cells.
Interleukin-33 (IL-33), a pro-inflammatory cytokine of the IL-1 family, is constitutively expressed in airway epithelial cells. Extracellular IL-33 plays central roles in Th2-type inflammatory responses associated with the development of asthma. However, the mechanisms regulating the expression and the release of IL-33 in asthma are largely unknown.
We found that purified YKL-40 protein attenuated the expression of IL-33 mRNA in Beas-2B cells. Interestingly, stable overexpression of YKL-40 in Beas-2B cells suppressed not only the constitutive expression of IL-33 mRNA, but also the increased IL-33 mRNA by Alternaria extracts, where protease activates PAR-2. Furthermore, stable suppression of PAR-2 expression by siRNA increased IL-33 mRNA levels and PAR-2 agonist peptide attenuated the expression of IL-33 mRNA in Beas-2B cells.
These findings suggest that YKL-40-induced IL-33 downregulation through PAR-2 in airway epithelial cell may be effective for preventing the development of asthma.
