||<Original article> Regulation of TSLP expression in human lung fibroblasts : the involvement of TNF-α TGF-β, FGF-2, and ATP
Yamamoto, Takanori ,
Koizumi, Schuichi ,
Masuyama, KeisukeNakao, Atsuhito
25 , 2017 , 山梨大学医学会
Thymic stromal lymphopoietin (TSLP) plays a central role in the development of Th2-type allergic infl ammation and epithelial cells are thought to be a major source of TSLP at the sites of allergic infl ammation. This study investigated whether TSLP is also expressed in stromal cells, such as lung fi broblasts and, if so, how it is regulated. Primary human lung fi broblasts produced substantial amounts of TSLP in response to TNF-α , which was augmented by the Th2 cytokines IL-4 and IL-13 and suppressed by BAY 11-7082, an NF-κ B inhibitor. Pretreatment of human lung fi broblasts with TGF-β or FGF-2 inhibited both TNF-α - and TNF-α plus IL-13-induced TSLP production. Furthermore, human lung fi broblasts produced TSLP in response to a conditioned medium derived from human bronchial epithelial cell cultures stimulated by polyI: C or cigarette smoke extract in a TNF-α -dependent manner. Interestingly, there was an increase in the TSLP production in human lung fi broblasts incubated with un-stimulated conditioned medium obtained from bronchial epithelial cell cultures. This basal TSLP expression was inhibited by suramin, a broad-range purinergic receptor antagonist. Consistently, the unstimulated conditioned medium contained substantial amounts of ATP and exogenous ATP induced TSLP production in human lung fi broblasts. Collectively, TSLP production by human lung fi broblasts was positively regulated by TNF-α (in synergy with IL-4 or IL-13) or ATP released from human bronchial epithelial cells, and negatively regulated by TGF-β or FGF-2. Human lung fi broblasts may therefore play an additional role in the development of allergic airway infl ammation via TSLP production and in cooperationwith bronchial epithelial cells.