title: Thymic stromal lymphopoietin is expressed and produced by caspase-1/NF-κB pathway in mast cells.
abstract: Thymic stromal lymphopoietin (TSLP) plays a pivotal role in allergic diseases such as atopic dermatitis, asthma, and chronic obstructive pulmonary disease. Although there are many reports regarding function and regulatory mechanism of TSLP in dendritic cells and/or T cells, the regulatory mechanism of TSLP in mast cells has not been fully elucidated. Here, we describe how TSLP is expressed and produced by inflammatory stimulus in mast cells. TSLP mRNA was expressed by phorbol myristate acetate (PMA) plus A23187 stimulation in HMC-1 cells and reached its peak 5h after PMA plus A23187 stimulation. The expression of TSLP mRNA was inhibited by nuclear factor (NF)-κB inhibitor. In addition, NF-κB luciferase activity was inhibited by caspase-1 inhibitor, indicating that caspase-1 is an upstream of NF-κB in mast cells. Furthermore, caspase-1 inhibitor decreased the expression of TSLP mRNA induced by PMA plus A23187. Finally, TSLP production was inhibited by both caspase-1 inhibitor and NF-κB inhibitor. These results provide proof of principle that TSLP can be expressed and produced through caspase-1 and NF-κB in mast cells and open new perspectives to pharmacologically manipulate the expression and production of TSLP by molecules acting on the caspase-1 and NF-κB pathway.
authors.affiliation: Department of Pharmacology, College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Phil-Dong
authors.initials: PD
authors.lastname: Moon
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000001:Calcimycin / Q000494:pharmacology; D020170:Caspase 1 / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007476:Ionophores / Q000494:pharmacology; D008407:Mast Cells / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D007476:Ionophores; D016328:NF-kappa B; D012333:RNA, Messenger; D000001:Calcimycin; D020170:Caspase 1; D013755:Tetradecanoylphorbol Acetate; D000094632:Thymic Stromal Lymphopoietin