Oxymatrine Sensitizes the HaCaT Cells to the IFN-γ Pathway and Downregulates MDC, ICAM-1, and SOCS1 by Activating p38, JNK, and Akt

Abstract

Decreased interferon (IFN)-γ levels and increased levels of macrophage-derived chemokine (MDC) and intercellular adhesion molecule (ICAM)-1 are known to be involved in allergic skin diseases, such as eczema and atopic dermatitis. Activation of the IFN-γ and its downstream interleukin-12 (IL-12) pathway can correct these diseases. Suppressor of cytokine signaling 1 (SOCS1) is a cytokine signaling inhibitor that blocks downstream pathways of IFN-γ by blocking the mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) signaling pathways. Oxymatrine (OMT), a quinolizidine alkaloid extracted from the herbal medicine Radix Sophorae flavescentis, is used to treat allergic skin diseases in China. The non-cytotoxic concentrations of OMT in HaCaT cells were determined through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Tumor necrosis factor (TNF)-α and IFN-γ were used to stimulate HaCaT cells, and OMT was added to this system with tacrolimus (FK506) as a positive control. The mRNAs of cytokines, MDC, ICAM-1, IL-12p35, IL-12p40, and IFN-γ receptor (IFN-γR)α were detected by RT-PCR. Western blot analyses were performed to assess activation of the MAPK (p38, Jun N-terminal kinase, and extracellular signal-regulated kinase) and Akt signaling pathways. OMT increased the mRNA levels of the IL-12 and IFN-γRα, reduced the mRNA levels of ICAM-1, MDC, and SOCS1. But FK506 increased the mRNA levels of IL12 and inhibited the expression of ICAM-1 mRNAs and had no effects on the IFN-γRα, MDC, and SOCS1 mRNA in HaCaT cells stimulated with TNF-α and IFN-γ. Thus, the mechanisms through which OMT and FK506 ameliorate allergic skin diseases differ.

Quantitative and bioinformatics integrated strategy to investigate the pharmacological mechanism of Ermiao Wan against eczema

“…MMP9 may be directly related to the pathogenesis and development of eczema, as it may affect the susceptibility to eczema by degrading COL5A3 [36]. Moreover, the downregulation of ICAM-1 and AKT expression via activation of MAPK8 and JNK has been shown as one of the mechanisms in the treatment of eczema [37]. These targets play an important role in the pathogenesis of eczema; thus, drug interventions targeting these genes can be effective for eczema treatment.…”

Inhibitory Effects of Helianthus tuberosus Ethanol Extract on Dermatophagoides farina body-induced Atopic Dermatitis Mouse Model and Human Keratinocytes

“…It has long been known that pathological cell adhesion is observed between nerve fibers and mast cells in AD skin lesions [ 37 ]. ICAM-1, VCAM-1, and selectins are closely related to allergic skin diseases and their levels are consequentially increased in the epidermis of patients with AD; Th2 cytokines are recruited to the inflamed site by these inflammatory factors [ 38 ]. In the present study, we found that HT treatment reduced the protein levels of adhesion molecules in Dfb-induced AD mice model ( Figure 4 ).…”

Oxymatrine exerts protective effects on osteoarthritis via modulating chondrocyte homoeostasis and suppressing osteoclastogenesis

“…Furthermore, OMT accelerates cancer cell apoptosis and reverses multidrug resistance when combined with other chemotherapeutic drugs . The anti‐inflammation effects of OMT appear to involve both inhibition of MAPK phosphorylation and reduce the activation of the NF‐κB signalling pathway . Furthermore, OMT exhibits substantial therapeutic potential for the treatment of myocardial diseases through modulating of the JAK2/STAT3 and TGF‐β1/Smad3 signalling pathway, but the effects of OMT on the onset and progression of OA have not been reported, to our knowledge.…”