The Experts below are selected from a list of 537 Experts worldwide ranked by ideXlab platform

Zhu Shen - One of the best experts on this subject based on the ideXlab platform.

  • mtorc2 pkbα akt1 serine 473 phosphorylation axis is essential for regulation of foxp3 stability by chemokine ccl3 in Psoriasis
    Journal of Investigative Dermatology, 2013
    Co-Authors: Ling Chen, Eric Pier, Yun Zhao, Zhu Shen
    Abstract:

    The connection between infections and acute Guttate Psoriasis (AGP) outbreaks/chronic plaque Psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3+Tregs in Psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4+CD25+T cells of patients with Psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKBα/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3+Tregs and the development of Psoriasis.

  • mTORC2-PKBα/Akt1 Serine 473 phosphorylation axis is essential for regulation of FOXP3 Stability by chemokine CCL3 in Psoriasis.
    The Journal of investigative dermatology, 2012
    Co-Authors: Ling Chen, Eric Pier, Yun Zhao, Zhu Shen
    Abstract:

    The connection between infections and acute Guttate Psoriasis (AGP) outbreaks/chronic plaque Psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3+Tregs in Psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4+CD25+T cells of patients with Psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKBα/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3+Tregs and the development of Psoriasis.

Ling Chen - One of the best experts on this subject based on the ideXlab platform.

  • mtorc2 pkbα akt1 serine 473 phosphorylation axis is essential for regulation of foxp3 stability by chemokine ccl3 in Psoriasis
    Journal of Investigative Dermatology, 2013
    Co-Authors: Ling Chen, Eric Pier, Yun Zhao, Zhu Shen
    Abstract:

    The connection between infections and acute Guttate Psoriasis (AGP) outbreaks/chronic plaque Psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3+Tregs in Psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4+CD25+T cells of patients with Psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKBα/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3+Tregs and the development of Psoriasis.

  • mTORC2-PKBα/Akt1 Serine 473 phosphorylation axis is essential for regulation of FOXP3 Stability by chemokine CCL3 in Psoriasis.
    The Journal of investigative dermatology, 2012
    Co-Authors: Ling Chen, Eric Pier, Yun Zhao, Zhu Shen
    Abstract:

    The connection between infections and acute Guttate Psoriasis (AGP) outbreaks/chronic plaque Psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3+Tregs in Psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4+CD25+T cells of patients with Psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKBα/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3+Tregs and the development of Psoriasis.

Yun Zhao - One of the best experts on this subject based on the ideXlab platform.

  • mtorc2 pkbα akt1 serine 473 phosphorylation axis is essential for regulation of foxp3 stability by chemokine ccl3 in Psoriasis
    Journal of Investigative Dermatology, 2013
    Co-Authors: Ling Chen, Eric Pier, Yun Zhao, Zhu Shen
    Abstract:

    The connection between infections and acute Guttate Psoriasis (AGP) outbreaks/chronic plaque Psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3+Tregs in Psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4+CD25+T cells of patients with Psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKBα/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3+Tregs and the development of Psoriasis.

  • mTORC2-PKBα/Akt1 Serine 473 phosphorylation axis is essential for regulation of FOXP3 Stability by chemokine CCL3 in Psoriasis.
    The Journal of investigative dermatology, 2012
    Co-Authors: Ling Chen, Eric Pier, Yun Zhao, Zhu Shen
    Abstract:

    The connection between infections and acute Guttate Psoriasis (AGP) outbreaks/chronic plaque Psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3+Tregs in Psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4+CD25+T cells of patients with Psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKBα/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3+Tregs and the development of Psoriasis.

Eric Pier - One of the best experts on this subject based on the ideXlab platform.

  • mtorc2 pkbα akt1 serine 473 phosphorylation axis is essential for regulation of foxp3 stability by chemokine ccl3 in Psoriasis
    Journal of Investigative Dermatology, 2013
    Co-Authors: Ling Chen, Eric Pier, Yun Zhao, Zhu Shen
    Abstract:

    The connection between infections and acute Guttate Psoriasis (AGP) outbreaks/chronic plaque Psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3+Tregs in Psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4+CD25+T cells of patients with Psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKBα/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3+Tregs and the development of Psoriasis.

  • mTORC2-PKBα/Akt1 Serine 473 phosphorylation axis is essential for regulation of FOXP3 Stability by chemokine CCL3 in Psoriasis.
    The Journal of investigative dermatology, 2012
    Co-Authors: Ling Chen, Eric Pier, Yun Zhao, Zhu Shen
    Abstract:

    The connection between infections and acute Guttate Psoriasis (AGP) outbreaks/chronic plaque Psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3+Tregs in Psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4+CD25+T cells of patients with Psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKBα/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3+Tregs and the development of Psoriasis.

Laurence Le Cleach - One of the best experts on this subject based on the ideXlab platform.

  • Non-antistreptococcal interventions for acute Guttate Psoriasis or an acute Guttate flare of chronic Psoriasis
    Cochrane database of systematic reviews (Online), 2019
    Co-Authors: Annabel Maruani, Mahtab Samimi, Natasha Stembridge, Rania Abdel Hay, Elsa Tavernier, Carolyn Hughes, Laurence Le Cleach
    Abstract:

    BACKGROUND: Guttate Psoriasis displays distinctive epidemiological and clinical features, making it a separate entity within the heterogeneous group of cutaneous Psoriasis types. It is associated with genetic, immune, and environmental factors (such as stress and infections) and usually arises in younger age groups (including children, teenagers, and young adults). There is currently no cure for Psoriasis, but various treatments can help to relieve the symptoms and signs. The objectives of treatment when managing an acute flare of Guttate Psoriasis are to reduce time to clearance and induction of long-term remission after resolution. This is an update of a Cochrane Review first published in 2000; since then, new treatments have expanded the therapeutic spectrum of systemic treatments used for Psoriasis. OBJECTIVES: To assess the effects of non-antistreptococcal interventions for acute Guttate Psoriasis or an acute Guttate flare of chronic Psoriasis. SEARCH METHODS: We searched the following databases up to June 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials. We checked the proceedings of key dermatology conferences from 2004 to 2018, and also searched for trials in the US Food and Drug Administration (FDA) database for drug registration. SELECTION CRITERIA: All randomised controlled trials assessing the effects of treatments for acute Guttate Psoriasis or an acute Guttate flare of chronic Psoriasis clinically diagnosed in children and adults. This included all topical and systemic drugs, biological therapy, phototherapy (all forms: topical and systemic), and complementary and alternative therapies. We compared these treatments against placebo or against another treatment. We did not include studies on drugs that aim to eradicate streptococcal infection. We did not include studies when separate results for Guttate Psoriasis participants were not available. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and methodological quality and extracted data. We used standard methodological procedures expected by Cochrane. Our primary outcomes were 'percentage of participants clear or almost clear (i.e. obtaining Psoriasis Area Severity Index (PASI) 100/90 and/or Physician's Global Assessment (PGA) of 0 or 1)' and 'percentage of participants with adverse effects and severe adverse effects'. Our secondary outcomes were 'number of relapses of Guttate Psoriasis or flares within a period of six months after the treatment has finished', 'percentage of participants achieving a PASI 75 or PGA of 1 or 2', and 'improvement in participant satisfaction measures and quality of life assessment measures'. We used GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS: This review included only one trial (21 participants), which compared fish oil-derived (n-3) fatty acid-based lipid emulsion (50 mL per infusion (1.05 g eicosapentaenoic and 10.5 g docosahexaenoic acid)) (10 participants) to soya oil-derived (n-6) fatty acid-based lipid emulsion (50 mL per infusion (1.05 g eicosapentaenoic and 10.5 g docosahexaenoic acid)) (11 participants) administered intravenously twice daily for 10 days, with a total follow-up of 40 days. The study was conducted in a single centre in Germany in 18 men and three women, aged between 21 and 65 years, who were in hospital with acute Guttate Psoriasis and had mean total body surface involvement of 25.7% ± 20.4% (range 10 to 90). The study was funded by a company that produces the oil emulsions. We found no other evidence regarding non-antistreptococcal interventions used in clinical practice for Guttate Psoriasis, such as topical treatments (corticosteroids, vitamin D₃ analogues), systemic drugs, biological therapy, and phototherapy.The primary outcomes of the review were not measured, and only one of our secondary outcomes was measured: improvement in participant satisfaction measures and quality of life assessment measures. However, the study authors did report that there was rare skin irritation at the site of peripheral intravenous route, but the number of affected participants was not provided.Improvement between baseline and day 10, using a non-validated score assessed by participants themselves daily based on five items (appearance of lesions, impairment of daily life, pruritus, burning, and pain), was greater in the group that received the fish oil-derived (n-3) fatty acid-based lipid emulsion (75%) than in the group receiving the soya oil-derived (n-6) fatty acid-based lipid emulsion (18%) (one trial, 21 participants). However, these results are uncertain as they are based on very low-quality evidence. AUTHORS' CONCLUSIONS: There is no evidence regarding topical and systemic drugs, biotherapy, or phototherapy in Guttate Psoriasis (we did not consider drugs that aimed to eradicate streptococcal infection because these are assessed in another Cochrane Review). We are uncertain of the effect of intravenously administered lipid emulsion on Guttate Psoriasis because the quality of the evidence is very low, due to risk of bias (unclear risk of bias for all domains), indirectness (the trial only included adults, and the follow-up from baseline was only 10 days), and imprecision (small number of participants).This review highlights the need for trials assessing the efficacy and safety of phototherapy and topical and systemic drugs for Guttate Psoriasis. There is also a need for studies that clearly distinguish the specific population with Guttate Psoriasis from the larger group of people with chronic plaque Psoriasis, and children and young adults should be assessed as a distinct group.