title: Alantolactone from Saussurea lappa Exerts Antiinflammatory Effects by Inhibiting Chemokine Production and STAT1 Phosphorylation in TNF-α and IFN-γ-induced in HaCaT cells.
abstract: Skin inflammation is the most common condition seen in dermatology practice and can be caused by various allergic reactions and certain toxins or chemicals. In the present study, we investigated the antiinflammatory effects of Saussurea lappa, a medicinal herb, and its marker compounds alantolactone, caryophyllene, costic acid, costunolide, and dehydrocostuslactone in the HaCaT human keratinocyte cell line. HaCaT cells were stimulated with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and treated with S. lappa or each of five marker compounds. Chemokine production and expression were analyzed by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction, respectively. Phosphorylation of signal transducer and activator of transcription (STAT) 1 was determined by immunoblotting. Stimulation with TNF-α and IFN-γ significantly increased the production of the following chemokines: thymus-regulated and activation-regulated chemokine (TARC): regulated on activation, normal T-cell expressed and secreted (RANTES): macrophage-derived chemokine (MDC): and interleukin-8 (IL-8). By contrast, S. lappa and the five marker compounds significantly reduced the production of these chemokines by TNF-α and IFN-γ-treated cells. S. lappa and alantolactone suppressed the TNF-α and IFN-γ-stimulated increase in the phosphorylation of STAT1. Our results demonstrate that alantolactone from S. lappa suppresses TNF-α and IFN-γ-induced production of RANTES and IL-8 by blocking STAT1 phosphorylation in HaCaT cells.
authors.affiliation: K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, 305-811, Korea.|Division of Allergy and Chronic Respiratory Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Chungcheongbuk-do, 361-951, Korea.
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Lim
authors.affiliation: K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, 305-811, Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Jin
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, 305-811, Korea.
authors.forename: Ohn-Soon
authors.initials: OS
authors.lastname: Kim
authors.affiliation: K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, 305-811, Korea.
authors.forename: Hyeun-Kyoo
authors.initials: HK
authors.lastname: Shin
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, 305-811, Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D054414:Chemokine CCL17 / Q000378:metabolism; D054422:Chemokine CCL22 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects; D007783:Lactones / Q000494:pharmacology*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D000081223:Polycyclic Sesquiterpenes; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050799:STAT5 Transcription Factor; D030441:Saussurea / Q000737:chemistry*; D012717:Sesquiterpenes / Q000494:pharmacology; D045787:Sesquiterpenes, Eudesmane / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D025521:Tumor Suppressor Proteins
chemical_list: D000893:Anti-Inflammatory Agents; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D018946:Chemokine CCL5; D018925:Chemokines; D016209:Interleukin-8; D007783:Lactones; D010936:Plant Extracts; D000081223:Polycyclic Sesquiterpenes; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D012717:Sesquiterpenes; D045787:Sesquiterpenes, Eudesmane; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; C083030:dehydrocostus lactone; C002602:costunolide; D007371:Interferon-gamma; C024714:caryophyllene; C004363:alantolactone
keywords: STAT1; Saussurea lappa; alantolactone; chemokines; keratinocytes