Down-regulation of transforming growth factor-beta receptors I and II is seen in lesional but not non-lesional psoriatic epidermis

Leivo,; Kariniemi,; Keski-Oja,; Virtanen, A.

doi:10.1046/j.1365-2133.1998.02026.x

Cited by 30 publications

(19 citation statements)

References 34 publications

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“…Another study showed a correlation of disease severity with concentrations of TGF-β1 in psoriatic scales (Flisiak et al , 2002). Several other studies, however, have shown a negative or absent correlation of expression of TGF-β1 or its receptors in psoriasis (Leivo et al , 1998; Doi et al , 2003). These published studies are insufficient to determine definitely whether there is a positive or negative correlation between TGF-β1 and psoriasis.…”

Section: Discussionmentioning

confidence: 90%

Inflammatory Skin Disease in K5.hTGF-β1 Transgenic Mice Is Not Dependent on the IL-23/Th17 Inflammatory Pathway

Fitch

Rizzo

Kurtz³

et al. 2009

Journal of Investigative Dermatology

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In the presence of IL-6, transforming growth factor (TGF)-β1 induces differentiation of T helper (Th) 17 cells in mice. Interleukin (IL)-23, a heterodimeric cytokine composed of IL-23p19 and IL-12/23p40 subunits, stimulates the growth and expansion of Th17 cells, and has been implicated in psoriasis pathogenesis. To study the associations between TGF-β1, the IL-23/Th17 inflammatory pathway, and psoriasis, we investigated inflammatory skin disease in transgenic mice that constitutively overexpress human TGF-β1 in basal keratinocytes (K5.hTGF-β1 transgenic mice); these mice had previously been reported as having a psoriasis-like disease. K5.hTGF-β1 transgenic mice had high levels of TGF-β1 mRNA and protein in both skin and serum. Levels of cytokines involved in IL-23/Th17-mediated inflammation were not elevated in lesional skin compared with those in non-lesional and wild-type skin. It is noteworthy that IL-4 and IgE were markedly elevated in inflamed skin and serum, respectively, of transgenic mice. Monoclonal antibodies (mAbs) specifically directed against IL-23p19 or IL-12/23p40 had no clinical effect on established inflammatory skin disease in K5.hTGF-β1 transgenic mice, whereas the same mAbs were able to block the development of murine experimental autoimmune encephalomyelitis, an IL-23/Th17-mediated disease. In summary, the IL-23/Th17 inflammatory pathway is not responsible for the maintenance of inflammatory skin disease in K5.hTGF-β1 transgenic mice.

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Section: Discussionmentioning

confidence: 90%

Inflammatory Skin Disease in K5.hTGF-β1 Transgenic Mice Is Not Dependent on the IL-23/Th17 Inflammatory Pathway

Fitch

Rizzo

Kurtz³

et al. 2009

Journal of Investigative Dermatology

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“…Psoriasis activity can be related to an imbalance between stimulation and inhibition of keratinocyte proliferation by these bioactive compounds. One of the most important inhibitors of epithelial cell proliferation is transforming growth factor (TGF)-b 1 , a strong stimulus for tissue inhibitors of metalloproteinases (TIMP), affecting the activity of extracellular matrix metalloproteinases (MMP) responsible for collagen degradation (Wataya-Kaneda et al 1996, Furue et al 1997, Wang et al 1997, Leivo et al 1998, Flisiak et al 2005. TGF-b 1 gene polymorphism may be important for the type of psoriasis (Baran et al 2007).…”

Section: Please Scroll Down For Articlementioning

confidence: 99%

Plasma TGF-β₁, TIMP-1, MMP-1 and IL-18 as a combined biomarker of psoriasis activity

2008

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Plasma levels of transforming growth factor (TGF)-beta1, tissue inhibitors of metalloproteinases (TIMP)-1, matrix metalloproteinase (MMP)-1 and interleukin (IL)-18 when analyzed separately demonstrate an association with psoriasis severity and treatment efficacy. To determine the highest correlation with the Psoriasis Area and Severity Index (PASI) score we carried out an analysis of these four proteins combined as the TTMI score. Concentrations of proteins were measured using an enzyme immunoassay in the plasma of 32 patients with chronic plaque-type psoriasis. The concentration of each biomarker was multiplied by the respective coefficient and the final individual TTMI score was the sum of these four values. TGF-beta1, TIMP-1 and IL-18 demonstrated significant positive correlation, whereas MMP-1 demonstrated significant negative correlation with the PASI score. The TTMI score calculated for individual patients varied from -79620 to 145713 (43050+/-8081) and demonstrated significant correlation with the PASI score. The lowest TTMI mean value was observed in patients with a PASI score <16 and the highest value was in patients with a PASI score >20. The combined measurement of plasma TGF-beta1, TIMP-1, MMP-1 and IL-18 has superior value as a biomarker of psoriasis activity in comparison with their separate analysis.

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“…In human psoriasis, there is a significant reduction of TGFβ receptors in psoriatic epidermis (Leivo et al, 1998;Doi et al, 2003). Since TGFβ1 is a potent growth inhibitor for keratinocytes, it has been suspected that reduced TGFβ signaling potentiates keratinocyte hyperproliferation in psoriasis epidermis.…”

Section: Alteration Of Tgfβ1 In Human Psoriasismentioning

confidence: 99%

A Role for TGFβ Signaling in the Pathogenesis of Psoriasis

Han

Williams

Salter

et al. 2010

Journal of Investigative Dermatology

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Dysregulation of transformation growth factor β (TGFβ) signaling has been reported in human psoriasis. However, the causal role of TGFβ in psoriasis has not been given attention until our recent report that the transgenic mice expressing wild-type TGFβ1 in the epidermis using a keratin 5 promoter (K5.TGFβ1wt) developed psoriasis-like skin inflammation. Additional experimental data further support the causal role of TGFβ1 overexpression in psoriasis. First, we temporally induced TGFβ1 expression in keratinocytes in our gene-switch-TGFβ1wt transgenic mice and found that inflammation severity correlated with on-and-off switch of TGFβ1wt transgene expression. Second, deletion of T cells in K5.TGFβ1wt mice significantly delayed the development of psoriatic lesions. Third, therapeutic approaches effective for human psoriasis, i.e. Enbrel and Rosiglitazone (Avandia®), are also effective in relieving the symptoms seen in K5.TGFβ1wt mice. Future studies will dissect specific mechanisms and identify key factors in the TGFβ1-induced skin inflammation. Our mouse models will provide a useful tool to test novel therapeutic interventions and help to design specific therapeutic approaches for inflammatory skin disorders, including human psoriasis.

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Down-regulation of transforming growth factor-beta receptors I and II is seen in lesional but not non-lesional psoriatic epidermis

Cited by 30 publications

References 34 publications

Inflammatory Skin Disease in K5.hTGF-β1 Transgenic Mice Is Not Dependent on the IL-23/Th17 Inflammatory Pathway

Inflammatory Skin Disease in K5.hTGF-β1 Transgenic Mice Is Not Dependent on the IL-23/Th17 Inflammatory Pathway

Plasma TGF-β₁, TIMP-1, MMP-1 and IL-18 as a combined biomarker of psoriasis activity

A Role for TGFβ Signaling in the Pathogenesis of Psoriasis

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Down-regulation of transforming growth factor-beta receptors I and II is seen in lesional but not non-lesional psoriatic epidermis

Cited by 30 publications

References 34 publications

Inflammatory Skin Disease in K5.hTGF-β1 Transgenic Mice Is Not Dependent on the IL-23/Th17 Inflammatory Pathway

Inflammatory Skin Disease in K5.hTGF-β1 Transgenic Mice Is Not Dependent on the IL-23/Th17 Inflammatory Pathway

Plasma TGF-β1, TIMP-1, MMP-1 and IL-18 as a combined biomarker of psoriasis activity

A Role for TGFβ Signaling in the Pathogenesis of Psoriasis

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Product

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Plasma TGF-β₁, TIMP-1, MMP-1 and IL-18 as a combined biomarker of psoriasis activity