Suppression of Th2-driven, allergen-induced airway inflammation by sauchinone.
Sauchinone, a lignan compound isolated from the root of Saururus chinensis, has been recently demonstrated to exhibit anti-inflammatory activity via the suppression of NF-kB p65 activity in vitro. In an effort to evaluate the in vivo anti-inflammatory function of sauchinone, we have evaluated the effects of sauchinone on allergen-induced airway inflammation using a murine model of allergic asthma. We observed that marked eosinophilic and lymphocyte infiltration in the BAL fluid were suppressed to a significant degree by sauchinone, and that mucus-secreting goblet cell hyperplasia and collagen deposition in the airways were also ameliorated by administration of sauchinone treatment. Moreover, gene expression of the inflammatory cytokines, IL-13, and IL-5 and eotaxin in the lung, and IL-5 in the draining lymph node were significantly decreased in sauchinone-treated mice. We demonstrated that sauchinone repressed Th2 cell development in vitro and IL-4 production by Th2 cells, and also inhibited GATA-3-mediated IL-5 promoter activity in a dose-dependent manner. Collectively, sauchinone ameliorated allergen-induced airway inflammation, in part, by repressing GATA-3 activity for Th2 cell development, indicating the possible therapeutic potential of sauchinone in airway inflammatory diseases including allergic asthma and rhinitis.
Min
Hyun Jung
HJ
College of Pharmacy and Division of Life and Pharmaceutical Sciences and Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Republic of Korea.
Won
Hee Yeon
HY
Kim
Young Choong
YC
Sung
Sang Hyun
SH
Byun
Mi Ran
MR
Hwang
Jun-Ha
JH
Hong
Jeong-Ho
JH
Hwang
Eun Sook
ES
D000485:Allergens; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001578:Benzopyrans / Q000627:therapeutic use*; D054413:Chemokine CCL11 / Q000235:genetics; D004149:Dioxoles / Q000627:therapeutic use*; D050990:GATA3 Transcription Factor / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism; D007165:Immunosuppression Therapy; D018793:Interleukin-13 / Q000235:genetics; D019409:Interleukin-15 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D000485:Allergens; D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D004149:Dioxoles; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018793:Interleukin-13; D019409:Interleukin-15; D015848:Interleukin-5; C410958:sauchinone; D015847:Interleukin-4