Sulforaphane suppresses TARC/CCL17 and MDC/CCL22 expression through heme oxygenase-1 and NF-κB in human keratinocytes

• Published in: Archives of pharmacal research 2010, 33(11), , pp.1867-1876
• Main Authors: Jeong, Seung-Il, Choi, Byung-Min, Jang, Seon Il
• Format: Article
• Language: English
• Subjects: Brassica; Chemokine CCL17 - metabolism; Chemokine CCL22 - genetics; Chemokine CCL22 - metabolism; Chemokines, CC - genetics; Chemokines, CC - metabolism; Chemoprevention; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - pathology; Gene Expression Regulation - drug effects; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Humans; Interferon-gamma - genetics; Interferon-gamma - metabolism; Isothiocyanates; Keratinocytes - drug effects; Keratinocytes - metabolism; Medicine; NF-kappa B - genetics; NF-kappa B - metabolism; Pharmacology/Toxicology; Pharmacy; Phytotherapy; Signal Transduction - drug effects; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - metabolism; Thiocyanates - metabolism; Thiocyanates - pharmacology; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-010-1120-6

Sulforaphane (4-methylsulfinylbutyl isothiocyanate, SFN) from broccoli has been used a chemopreventive photochemical as detoxification of xenobiotics and anti-inflammatory, however, there is no studies for Th2 chemokine expression through heme oxygenase-1 and NF-κB in keratinocytes. Atopic dermatitis is a chronically relapsing pruritic inflammatory skin disease. SFN is demonstrated to have anti-inflammatory and anti-oxidant effects. This study aimed to define whether and how SFN regulates Th2-related chemokine production in human HaCaT keratinocytes. The level of chemokine expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and signaling study was performed by Western blot analysis. Chemokine production was determined by enzyme-linked immunosorbent assay. Pretreatment with SFN suppressed interferon-γ (IFN-γ) and tumor necrosis factor (TNF)-α- induced thymus- and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) production in HaCaT keratinocytes. SFN inhibited IFN-γ and TNF-α-induced NF-κB activation as well as STAT1 activation. Interestingly, pretreatment with SFN result in significantly suppressed IFN-γ and TNF-α-induced TARC/CCL17 and MDC/CCL22 production through the induction of HO-1. This suppression was completely abolished by HO-1 siRNA. Furthermore, Carbon monoxide, but not other end products of HO-1 activity, also suppressed IFN-γ and TNF-α-induced TARC/CCL17 and MDC/CCL22 production. These results demonstrate that SFN has an inhibitory role in IFN-γ and TNF-α-induced production of TARC/CCL17 and MDC/CCL22 in human HaCaT cells by inhibition of NF-κB activation and induction of HO-1.