Cutting edge: Inhibition of NF-kappaB-mediated TSLP expression by retinoid X receptor.
The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) has important roles in the initiation of allergic airway inflammation and the activation of dendritic cells. We have shown that the human TSLP gene is regulated in a NF-kappaB-dependent manner; however the factors that negatively regulate TSLP expression are not known. In this study we demonstrate that 9-cis-retinoic acid (9-cis-RA) is a negative regulator of TSLP expression in airway epithelial cells. This inhibition is manifested as a block in the IL-1beta-mediated recruitment of NF-kappaB to the human TSLP promoter. 9-cis-RA-mediated inhibition is not restricted to TSLP gene expression but rather reflects a general inhibition of NF-kappaB activation, as other NF-kappaB-regulated-genes were also inhibited in a similar manner by 9-cis-RA treatment. Taken as a whole, these data demonstrate that inhibition of IL-1beta-dependent genes by active retinoid X receptors involves antagonism of NF-kappaB signaling.
Lee
Hai-Chon
HC
Immunology Program, Benaroya Research Institute, Seattle, WA 98101, USA.
Headley
Mark B
MB
Iseki
Masanori
M
Ikuta
Koichi
K
Ziegler
Steven F
SF
D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism; D047488:Retinoid X Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D014212:Tretinoin / Q000494:pharmacology; D000094632:Thymic Stromal Lymphopoietin
D000970:Antineoplastic Agents; D016207:Cytokines; D053583:Interleukin-1beta; D016328:NF-kappa B; D047488:Retinoid X Receptors; D000077556:Alitretinoin; D014212:Tretinoin; D000094632:Thymic Stromal Lymphopoietin