Role of <scp>NF</scp>‐κB in the pathogenesis of psoriasis elucidated by its staining in skin biopsy specimens

Moorchung, Nikhil; Kulaar, Janmeet S.; Chatterjee, Manas; Vasudevan, Biju; Tripathi, Tanu; Dutta, Vibha

doi:10.1111/ijd.12050

Cited by 51 publications

(47 citation statements)

References 27 publications

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“…The TNF-α-driven CCL20 release is mediated by keratinocytes and dermal fibroblasts [45]. Upregulation of these proinflammatory cytokines by TNF-α is facilitated through the activation of Nf-κB [46] – a transcription factor that is constitutively activated in psoriatic epidermis [47]. Elevated levels of Nf-κB facilitate keratinocyte hyperproliferation by inhibiting the cell cycle regulator protein, phosphatase 6, via the upregulation of the microRNA miR-31 [47].…”

Section: Resultsmentioning

confidence: 99%

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

2018

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Background: Psoriasis is a common, chronic inflammatory skin disorder, which can significantly impact quality of life. Despite major breakthroughs in our understanding of the pathogenesis of psoriasis, the chronological order of the underlying mechanisms leading to the development of psoriatic plaques remains to be completely understood. Summary: Although psoriasis is classically perceived as a T-cell disease, it is now well recognized that T lymphocytes do not function in exclusivity. This theory is supported by evidence from transgenic murine models that develop marked psoriasiform disease. In addition, immune cells and cytokines regulate both early and late events involved in the pathogenesis of psoriasis. Key Messages: Psoriasis is a complex disease – a dynamic interplay between immune cells, keratinocytes, and various other skin-resident cells, such as endothelial and immune cells. The contribution of each cell type is crucial in the initiation and maintenance phases of psoriatic alterations.

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Section: Resultsmentioning

confidence: 99%

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

2018

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“…Several studies have confirmed the presence of NF-κB activity in psoriatic (skin) disease (65),[65],[66]. However, in a human study, elevated active p65 was not reduced to normal baseline levels by TNF blockade, suggesting that TNF-independent NF-κB activity is present in psoriatic pathology [67].…”

Section: Molecular Pathways In Psa Pathogenesismentioning

confidence: 99%

The IL-23/IL-17 axis in psoriatic arthritis

Suzuki

Mellins

Gershwin

et al. 2014

Autoimmunity Reviews

146

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Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory disease, affecting both the skin and joints. Disease progression is associated with aberrant cytokine expression, and TNF blockade is the most successful therapy to date. However, not all patients are responsive to anti-TNF treatment, highlighting the need to better understand the cellular and molecular mechanisms that govern the disease. PsA associations with single nucleotide polymorphisms in IL23R as well as TRAF3IP2 (Act1), a molecule downstream of the IL-17 receptor (IL-17R), have linked the IL-23/IL-17 axis to disease pathology. Although both cytokines are implicated in PsA, a full picture of their cellular targets and pathogenic mechanisms has not yet emerged. In this review, we focus on the IL-23/IL-17 axis-elicited responses mediated by osteoclasts, keratinocytes and neutrophils. Expanding our understanding of the cellular and molecular mechanisms that dictate pathogenicity in PsA will contribute to developing novel treatment strategies to combat disease.

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“…VEGFR-2 could participate in the inflammatory process through p38, ERK1/2 and AKT pathway, which were upstream of NF-kB pathway. Besides, the activation of NF-kB could induce the production of inflammatory vascular markers (9). The mechanism by which HK exhibited anti-psoriatic effects maybe like this: HK inhibited VEGFR-2 signal through inhibition of p38, ERK1/2 and AKT, then inhibited the activation of NF-kB and inflammatory vascular markers.…”

Section: Discussionmentioning

confidence: 99%

“…Plasmacytoid dendritic cells (pDCs), infiltrating in psoriatic lesions, also exacerbated the Th17-mediated pathogenesis of psoriasis (7,8). Furthermore, NF-kB has been proved to be a crucial factor in the initiation of the inflammatory response of psoriasis (9). The classic form of NF-kB is the heterodimer of the p50 and p65 (RelA) subunits, which contains the transcriptional activation domain and sequestered in the cytoplasm as an inactive complex by the inhibitory proteins IkBs.…”

Section: Introductionmentioning

confidence: 99%

Anti-psoriatic effects of Honokiol through the inhibition of NF-κB and VEGFR-2 in animal model of K14-VEGF transgenic mouse

Wen

Pei

et al. 2015

Journal of Pharmacological Sciences

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Honokiol (HK), a biphenolic neolignan isolated from Magnolia officinalis, has been reported to possess anti-inflammatory and anti-angiogenic activaties. In this study, our aim was to investigate anti-psoriatic activities of HK and the involved mechanisms. In vitro, the effects of HK on the regulation of Th1/Th2 and TNF-α-induced NF-κB (p65) activation were analyzed by respective FCS and immunofluorescence. Additionally, the K14-VEGF transgenic model was used for the in vivo study. ELISA and Q-PCR were performed to evaluate serum levels of Th1/Th2 cytokines and their corresponding mRNA expressions. Effects on VEGFR-2 and p65 activation, as well as other angiogenic and inflammatory parameters were studied by immunostainings. Importantly, we found that HK significantly decreased the ratio of Th1/Th2-expression CD4(+) T cells and inhibited TNF-α-induced activation of NF-κB. The morphology and histological features of psoriasis were effectively improved by HK treatment. The expression of TNF-α and IFN-γ, and their corresponding mRNA levels were down-regulated and the expression of nuclear p65, VEGFR-2, as well as related phosphorylated proteins (p-VEGFR-2, p-ERK1/2, p-AKT and p-p38) were also suppressed. Overall, these results in our study suggested that HK exhibits anti-psoriatic effects through the inhibition of NF-κB and VEGFR-2.

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Role of NF‐κB in the pathogenesis of psoriasis elucidated by its staining in skin biopsy specimens

Cited by 51 publications

References 27 publications

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

The IL-23/IL-17 axis in psoriatic arthritis

Anti-psoriatic effects of Honokiol through the inhibition of NF-κB and VEGFR-2 in animal model of K14-VEGF transgenic mouse

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