Up-regulation of activities of mitogen-activated protein kinase in psoriatic lesions

Zhang, Xiaoyan; Yang, Dingquan; Ma, Shenglin; Huitu, Liu

doi:10.1016/j.jdermsci.2004.10.006

Cited by 4 publications

(5 citation statements)

References 4 publications

(5 reference statements)

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“…HaCaT cells in DMEM were seeded in 3-cm dishes a density of 0.5 × 10 6 cells/well and cultured for 24 h. The medium was replaced by adding 2 mL of FBS-free medium, and cells were cultured for 24 h. Then, cells were treated with OXY at 40 µM for 3 h, before stimulating with 100 ng/mL of TNF-α. Cell lysates were collected at different time points (0, 10,20,30,40,40,60,90,120,150,180, and 210 min) by adding 300 µL of 1× reducing Laemmli buffer. Next, the cell lysates were heated at 95 • C for 5 min, separated by SDS-PAGE using 10% gel, and transferred onto polyvinylidene difluoride (PVDF) membranes (GE Healthcare Life Science, Marlborough, MA, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Many studies have reported the aberrance of several elements of the PI3K/AKT signaling cascade in patients with psoriasis. One significant discovery demonstrated that PI3K is specifically overexpressed in psoriatic lesions in comparison with that in lesions of chronic dermatitis, seborrheic keratosis, squamous cell carcinoma, and basal cell carcinoma [30]. Additional research has provided information that phosphorylation of AKT is dominantly increased in the keratinocyte in psoriasis lesions in comparison with normal and non-lesional skin [31,32].…”

Section: Introductionmentioning

confidence: 99%

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Oxyresveratrol Inhibits TNF-α-Stimulated Cell Proliferation in Human Immortalized Keratinocytes (HaCaT) by Suppressing AKT Activation

et al. 2021

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Psoriasis is a complex inflammatory disease characterized by hyperproliferative keratinocyte caused by active PI3K/AKT signaling. TNF-α concentrated in the psoriatic lesions stimulates AKT activation. We previously discovered that oxyresveratrol inhibited inflammation via suppressing AKT phosphorylation, therefore oxyresveratrol may possess a conserved property to block AKT activation and proliferation in keratinocyte in response to TNF-α. Our current study proved that oxyresveratrol exhibited potent anti-proliferative effects against TNF-α. These effects are explained by the findings that oxyresveratrol could potentially inhibit TNF-α-stimulated AKT and GSK3-β activation in a dose-dependent manner, and its inhibitory pattern was comparable to that of a specific PI3K inhibitor. Results from immunofluorescence supported that oxyresveratrol effectively inhibited AKT and GSK3-β activation in individual cells upon TNF-α stimulation. Furthermore, functional assay confirmed that oxyresveratrol repressed the expansion of the HaCaT colony over 3 days, and this was caused by the ability of oxyresveratrol to induce cell cycle arrest at S and G2/M phases and the reduction in the expression of a proliferative marker (Ki-67) and a survival marker (MCL-1). Given the importance of TNF-α and the PI3K/AKT pathway in the psoriatic phenotype, we anticipate that oxyresveratrol, which targets the TNF-α-stimulated PI3K/AKT pathway, would represent a promising psoriasis therapy in the near future.

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Section: Western Blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxyresveratrol Inhibits TNF-α-Stimulated Cell Proliferation in Human Immortalized Keratinocytes (HaCaT) by Suppressing AKT Activation

et al. 2021

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“…Intracellular signaling systems such as Erk/JNK or MAP kinase, which are activated by the EGF family, are up-regulated in psoriatic epidermis [9]. Recent studies have shown that transgenic mice over-expressing a constitutive active form of STAT3 develop a psoriasis-like phenotype [10].…”

mentioning

confidence: 99%

Epiregulin, a member of the EGF family, is over-expressed in psoriatic epidermis

Shirakata

Kishimoto

Tokumaru

et al. 2007

Journal of Dermatological Science

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“…** P<0.01 vs. control. IL-22, interleukin 22; CK10, cytokeratin 10. the base layer and stratum spinosum cell nucleus, while in the normal skin p-ERK is only expressed in the basal layer (27). JNK and p38 kinase are expressed in the granular layer of the normal skin and in both the granular layer and stratum spinosum of the psoriatic lesions (28).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the activity of the MAPK signaling pathway is significantly increased in psoriatic lesions ( 26 ). Notably, in psoriasis, p-ERK is upregulated in the base layer and stratum spinosum cell nucleus, while in the normal skin p-ERK is only expressed in the basal layer ( 27 ). JNK and p38 kinase are expressed in the granular layer of the normal skin and in both the granular layer and stratum spinosum of the psoriatic lesions ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the effects of IL‑22 on the proliferation and differentiation of keratinocytes in�vitro

Liu

Yan

et al. 2020

Mol Med Rep

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Psoriasis is one of the most common chronic inflammatory skin diseases, it is characterized by hyperproliferation of keratinocytes and infiltration of inflammatory cells. Several in vitro studies have reported that interleukin (IL)-22 is involved in excessive proliferation and abnormal differentiation of human keratinocytes. However, the association between IL-22 and CCAAT enhancer binding protein α (C/EBPα) in the pathogenesis of psoriasis remains unclear. Therefore, the present study aimed to investigate the association between IL-22 and C/EBPα, and the effects of IL-22 on the proliferation and differentiation of keratinocytes. Keratinocytes were treated with different concentrations of IL-22 (30, 60 and 90 ng/ml) and subsequently cells were collected at different time intervals. The expression levels of the key molecules of the mitogen-activated protein kinase (MAPK) signaling pathway were detected using western blot analysis. In addition, the effect of IL-22 on the proliferation rate of keratinocytes and the mRNA expression levels of C/EBPα were determined using a Cell Counting Kit-8 assay and reverse transcription-quantitative PCR, respectively. Furthermore, keratinocytes were transfected with C/EBPα small interfering (si)RNA or control using Lipofectamine ® 2000. The results revealed that IL-22 significantly induced the proliferation of keratinocytes and the expression of phosphorylated (p)-JNK, pERK and p-p38 (P<0.05). Additionally, IL-22 significantly inhibited the differentiation of keratinocytes, and the mRNA and protein expression of C/EBPα (P<0.05). Furthermore, downregulation of C/EBPα increased the proliferation rate of keratinocytes and reduced the expression levels of cytokeratin 10 and involucrin. Therefore, these results suggested that the effect of IL-22 on the proliferation and differentiation of keratinocytes may be mediated via the regulation of the MAPK signaling pathway and the expression of C/EBPα.

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Up-regulation of activities of mitogen-activated protein kinase in psoriatic lesions

Cited by 4 publications

References 4 publications

Oxyresveratrol Inhibits TNF-α-Stimulated Cell Proliferation in Human Immortalized Keratinocytes (HaCaT) by Suppressing AKT Activation

Oxyresveratrol Inhibits TNF-α-Stimulated Cell Proliferation in Human Immortalized Keratinocytes (HaCaT) by Suppressing AKT Activation

Epiregulin, a member of the EGF family, is over-expressed in psoriatic epidermis

Evaluation of the effects of IL‑22 on the proliferation and differentiation of keratinocytes in�vitro

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