Ma Huang Tang Suppresses the Production and Expression of Inflammatory Chemokines via Downregulating STAT1 Phosphorylation in HaCaT Keratinocytes

Abstract

Ma huang tang (MHT) is a traditional herbal medicine comprising six medicinal herbs and is used to treat influenza-like illness. However, the effects of MHT on inflammatory skin diseases have not been verified scientifically. We investigated determining the inhibitory effects of MHT against inflammation responses in skin using HaCaT human keratinocyte cells. We found that MHT suppressed production of thymus and activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine (MDC/CCL22), regulated on activation of normal T-cell expressed and secreted (RANTES/CCL5), and interleukin-8 (IL-8) in tumor necrosis factor-α (TNF-α) and interferon-γ- (IFN-γ-) stimulated HaCaT cells. Consistently, MHT suppressed the mRNA expression of TARC, MDC, RANTES, and IL-8 in TNF-α and IFN-γ-stimulated cells. Additionally, MHT inhibited TNF-α and IFN-γ-stimulated signal transducer and activator of transcription 1 (STAT1) phosphorylation in a dose-dependent manner and nuclear translocation in HaCaT cells. Our finding indicates that MHT inhibits production and expression of inflammatory chemokines in the stimulated keratinocytes by downregulating STAT1 phosphorylation, suggesting that MHT may be a possible therapeutic agent for inflammatory skin diseases.

Laminaria japonica Suppresses the Atopic Dermatitis-Like Responses in NC/Nga Mice and Inflamed HaCaT Keratinocytes via the Downregulation of STAT1

“…We then examined the inhibitory effect of LJWE on the expression of inflammatory chemokines in TNF-α/IFN-γ-stimulated HaCaT cells. Consistent with the results of previous reports [ 24 , 26 ], co-stimulation with TNF-α/IFN-γ in HaCaT cells significantly increased the expression of TARC, RANTES, and IL-8 compared to the vehicle control ( p < 0.001). Additionally, LJWE significantly inhibited the expression of TARC, RANTES, and IL-8 in a dose-dependent manner ( p < 0.001) ( Figure 1 B).…”

“…These chemokines aggravate dermal inflammation by giving rise to AD-like skin lesions that are associated with the development and severity of AD. Stimulated keratinocytes secrete IL-8 resulting in the infiltration of T cells and neutrophils into the epidermis [24,25]. TARC and RANTES secreted by keratinocytes play an important role in the activation of macrophages and infiltration of T helper 2 cells in the inflamed tissues [5].…”

“…The expression of inflammatory chemokines, including TARC, RANTES, and IL-8 in TNF-α/IFN-γ-stimulated HaCaT cells was primarily regulated by MAPKs, NF-κB, and/or STAT signaling pathways [24,27,28]. NF-κB and STAT1, the important transcription factors that are activated by pro-inflammatory cytokines, that are present in the cytoplasm translocate into the nucleus and lead to the expression of several inflammatory chemokine and cytokine genes [29,30].…”

Shikonin Inhibits Der p 2‐Induced Cytokine and Chemokine Expression in Dendritic Cells in Patients with Atopic Dermatitis

“…Moreover, shikonin inhibited production of the proinflammatory cytokines IL-9, MIP-1 β , and RANTES more effectively than dexamethasone. In the recent year, CCL17 and CCL22 have been reported that played an important role in Th2 cytokines induced AD [ 42 ]. CCL17 and CCL22 could be secreted by dendritic cells not only developed the inflammatory responses but also became pivotal regulator of the AD pathogenesis.…”

Assessment of the Aromatase Inhibitory Activity of Ma-Huang-Tang (MHT) and Its Active Compounds

“…Traditional alternative medicine has the advantages of subject diversity and multiple active ingredients, and the use of alternative medicines, such as herbal medicines, which are known to contain active medicinal ingredients that have physiological effects on health, has increased [22,23]. Ma-Huang-Tang (MHT), an oriental herbal formula that has been used in Korea for a long time, is composed of six herbs, Ephedrae Herba, Cinnamomi Ramulus, Glycyrrhizae Radix et Rhizoma, Armeniacae Semen, Zingiberis Rhizoma Recens, and Allii Radix, and has traditionally been used in the treatment of sweating, asthma, febrile disease, and inflammatory skin diseases [24][25][26]. MHT also reportedly improves steroid-induced gene expression and ovarian dysfunction [27].…”