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

Abstract

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.

Induction of Peroxiredoxin 1 by Hypoxia Regulates Heme Oxygenase-1 via NF-κB in Oral Cancer

“…Studies have indicated that NF-κB induces expression of HO-1 in tumor tissues [28]–[31]. Moreover, numerous studies suggested a direct relationship between NF-κB and HO-1, but the function of NF-κB in regulating HO-1 expression in human cells is controversial [32]–[35]. In this study, our data showed that hypoxia induces Prx1 and NF-κB, and Prx1 regulates HO-1 via activating NF-κB.…”

Methyl 5-Chloro-4,5-didehydrojasmonate (J7) Inhibits Macrophage-Derived Chemokine Production <i>via</i> Down-Regulation of the Signal Transducers and Activators of Transcription 1 Pathway in HaCaT Human Keratinocytes

“…Some reports show that compounds or extract from natural product decrease the MDC production via inhibition of NF-κB and STAT1 activation. 33,34) Even though STAT1 and NF-κB signal were activated by IFN-γ and TNF-α in our condition, J7 only inhibited the activation of STAT1 signal. In RAW264.7 macrophages, J7 also inhibited the STAT1 activation, but not NF-κB, by LPS stimulation (Fig.…”

“…23,24) Furthermore, several plant extracts and compounds have been shown to inhibit the actions of inflammatory chemokines via the regulation of signaling pathways stimulated by IFN-γ and TNF-α, including STAT1, NF-κB, and mitogen-activated protein kinase (MAPK) cascades. [25][26][27][28] Among these transcription factors, the STAT1 protein is a crucial and specific regulator of IFN-γ-induced signals that controls the transcription of target genes, including MDC. 23,29) Therefore, we tested the effect of J7 on the activation of STAT1 in IFN-γ-and TNF-α-treated HaCaT keratinocytes and detected a high level of phosphorylated STAT1 at 15 min after cytokine treatment.…”

TWEAK/Fn14 Activation Participates in Ro52-Mediated Photosensitization in Cutaneous Lupus Erythematosus

“…Moreover, our results showed that keratinocytes express more CCL17 and CCL22 on TWEAK stimulation. CCL17 and CCL21 can be secreted by keratinocytes (36) and also contribute to the local recruitment of macrophages (37). The expression levels of CCL17 and CCL22 correlates with CCL19 in inflamed lungs, which further leads to the accumulation of macrophages (38).…”