Sulforaphane suppresses TARC/CCL17 and MDC/CCL22 expression through heme oxygenase-1 and NF-κB in human keratinocytes.
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.
Jeonju Biomaterials Institute, Korea.
Seung-Il
SI
Jeong
Byung-Min
BM
Choi
Seon Il
SI
Jang
D001937:Brassica; D054414:Chemokine CCL17 / Q000378:metabolism*; D054422:Chemokine CCL22 / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D018890:Chemoprevention; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D017879:Isothiocyanates; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D008517:Phytotherapy; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides; D013861:Thiocyanates / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
C106230:CCL17 protein, human; C515482:CCL22 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D017879:Isothiocyanates; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D013454:Sulfoxides; D013861:Thiocyanates; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D051547:Heme Oxygenase-1; C016766:sulforaphane