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Frontiers in Immunology 2022Psoriasis is a common inflammatory skin disease recognized by the World Health Organization as "an incurable chronic, noninfectious, painful, disfiguring and disabling...
INTRODUCTION
Psoriasis is a common inflammatory skin disease recognized by the World Health Organization as "an incurable chronic, noninfectious, painful, disfiguring and disabling disease." The fact that metabolic syndrome (MetS) is the most common and important comorbidities of psoriasis suggests an important role of lipid metabolism in the pathogenesis of psoriasis. Narciclasine (Ncs) is an alkaloid isolated from the Amaryllidaceae plants. Its biological activities include antitumor, antibacterial, antiinflammatory, anti-angiogenic and promoting energy expenditure to improve dietinduced obesity. Here, we report that Ncs may be a potential candidate for psoriasis, acting at both the organismal and cellular levels.
METHODS
The therapeutic effect of Ncs was assessed in IMQ-induced psoriasis-like mouse model. Then, through in vitro experiments, we explored the inhibitory effect of Ncs on HaCaT cell proliferation and Th17 cell polarization; Transcriptomics and lipidomics were used to analyze the major targets of Ncs; Single-cell sequencing data was used to identify the target cells of Ncs action.
RESULTS
Ncs can inhibit keratinocyte proliferation and reduce the recruitment of immune cells in the skin by inhibiting psoriasis-associated inflammatory mediators. In addition, it showed a direct repression effect on Th17 cell polarization. Transcriptomic and lipidomic data further revealed that Ncs extensively regulated lipid metabolismrelated genes, especially the Phospholipase A2 (PLA2) family, and increased antiinflammatory lipid molecules. Combined with single-cell data analysis, we confirmed that keratinocytes are the main cells in which Ncs functions.
DISCUSSION
Taken together, our findings indicate that Ncs alleviates psoriasiform skin inflammation in mice, which is associated with inhibition of PLA2 in keratinocytes and improved phospholipid metabolism. Ncs has the potential for further development as a novel anti-psoriasis drug.
Topics: Animals; Mice; Anti-Inflammatory Agents; Dermatitis; Group IV Phospholipases A2; Imiquimod; Lipid Metabolism; Phospholipids; Psoriasis
PubMed: 36700214
DOI: 10.3389/fimmu.2022.1094375 -
Wiener Medizinische Wochenschrift (1946) Sep 2023Comel-Netherton syndrome, or Netherton syndrome (NS), is a rare chronic genetic skin condition affecting the daily life of patients, which often results in poorly...
Comel-Netherton syndrome, or Netherton syndrome (NS), is a rare chronic genetic skin condition affecting the daily life of patients, which often results in poorly developed social skills and anxiety. Genetic predisposition plays a key role alongside the clinical findings, and clinicians must be aware of it as it can mimic other well-known skin conditions. Diagnosis is challenging both clinically and histologically. Clinically, it can mimic a severe form of atopic dermatitis, psoriasiform dermatitis overlapping with atopic dermatitis, or erythrokeratodermia variabilis. The difficulties in making histological diagnosis are similar, and it is often necessary to take several biopsies in order to clarify the diagnosis. Although retinoids are used for both psoriasis, erythrokeratodermia variabilis, and other congenital forms of keratodermia, the recommended treatment doses are different. This often results in poor treatment outcome. We present a 16-year-old patient previously diagnosed as erythrokeratodermia variabilis and treated with little to no improvement. Systemic therapy with acitretin 10 mg daily, local pimecrolimus 1%, emollients, and bilastine 20 mg once daily was initiated. Due to the limited application of retinoids and the difficulties in achieving permanent remission, modern medicine is faced with the challenge of seeking innovative therapeutic solutions. New hopes are placed on targeted or anti-cytokine therapy, based on inhibiting the inflammatory component of the disease. This article is mainly focused on innovative therapeutic options, including modern medications such as dupilumab, infliximab, secukinumab, anakinra, omalizumab, and others.
Topics: Humans; Adolescent; Dermatitis, Atopic; Netherton Syndrome; Erythrokeratodermia Variabilis; Bulgaria; Acitretin
PubMed: 36695942
DOI: 10.1007/s10354-022-00999-y -
The Journal of Allergy and Clinical... May 2023Psoriasis is a chronically relapsing inflammatory skin disease primarily perpetuated by skin-resident IL-17-producing T (T17) cells. Pellino-1 (Peli1) belongs to a...
BACKGROUND
Psoriasis is a chronically relapsing inflammatory skin disease primarily perpetuated by skin-resident IL-17-producing T (T17) cells. Pellino-1 (Peli1) belongs to a member of E3 ubiquitin ligase mediating immune receptor signaling cascades, including nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) pathway.
OBJECTIVE
We explored the potential role of Peli1 in psoriatic inflammation in the context of skin-resident T17 cells.
METHODS
We performed single-cell RNA sequencing of relapsing and resolved psoriatic lesions with analysis for validation data set of psoriasis. Mice with systemic and conditional depletion of Peli1 were generated to evaluate the role of Peli1 in imiquimod-induced psoriasiform dermatitis. Pharmacologic inhibition of Peli1 in human CD4 T cells and ex vivo human skin cultures was also examined to evaluate its potential therapeutic implications.
RESULTS
Single-cell RNA sequencing analysis revealed distinct T-cell subsets in relapsing psoriasis exhibiting highly enriched gene signatures for (1) tissue-resident T cells, (2) T17 cells, and (3) NF-κB signaling pathway including PELI1. Peli1-deficient mice were profoundly protected from psoriasiform dermatitis, with reduced IL-17A production and NF-κB activation in γδ T17 cells. Mice with conditional depletion of Peli1 treated with FTY720 revealed that Peli1 was intrinsically required for the skin-resident T17 cell immune responses. Notably, pharmacologic inhibition of Peli1 significantly ameliorated murine psoriasiform dermatitis and IL-17A production from the stimulated human CD4 T cells and ex vivo skin explants modeling psoriasis.
CONCLUSION
Targeting Peli1 would be a promising therapeutic strategy for psoriasis by limiting skin-resident T17 cell immune responses.
Topics: Mice; Humans; Animals; Interleukin-17; NF-kappa B; Psoriasis; Skin; Dermatitis; Disease Models, Animal; Nuclear Proteins; Ubiquitin-Protein Ligases
PubMed: 36646143
DOI: 10.1016/j.jaci.2022.12.823 -
Cutis Nov 2022
Topics: Humans; RNA, Messenger; COVID-19; Eczema; mRNA Vaccines
PubMed: 36638370
DOI: 10.12788/cutis.0656 -
The Malaysian Journal of Pathology Dec 2022Less biopsies were expected when large scale social restrictions were enforced during COVID-19 pandemic.
INTRODUCTION
Less biopsies were expected when large scale social restrictions were enforced during COVID-19 pandemic.
AIM
To compare the skin diseases prompting biopsy before and during the COVID-19 pandemic.
MATERIALS AND METHODS
A retrospective study of skin diseases was performed; the skin problems were then grouped into major histopathological reactions.
RESULTS
A total of 229 biopsies were performed before the COVID-19 outbreak, whereas only 160 biopsies were done during the pandemic. Before versus during the outbreak, the proportion of major reactions were granulomatous 20.52% vs 21.88%, neoplasms 17.47% vs 20%, psoriasiform 14.85% vs 10%, vesiculobullous 9.61% vs 8.75%, others 10.92% vs 7.50%, interface dermatitis 6.99% vs 10%, vasculopathy 6.99% vs 5.63%, spongiotic 6.55% vs 8.13%, panniculitis 3.49% vs 3.75%, and superficial and deep dermal infiltrate 2.62% vs 4.38%.
CONCLUSION
A decreased total number of patients prompting less biopsies were reported during the COVID-19 outbreak. However, the three largest percentages of major histopathological reactions were still similar, namely granulomatous, neoplasms, and psoriasiform.
Topics: Humans; Pandemics; Indonesia; Retrospective Studies; COVID-19; Skin Diseases; Biopsy
PubMed: 36591716
DOI: No ID Found -
Journal of Dermatological Science Nov 2022Few studies have addressed the impact of the psoriasis-related proinflammatory cytokines on the proliferation and melanogenesis of melanocytes (MCs) in lesional...
BACKGROUND
Few studies have addressed the impact of the psoriasis-related proinflammatory cytokines on the proliferation and melanogenesis of melanocytes (MCs) in lesional psoriatic skin.
OBJECTIVE
We investigated the effects of TNFα, IL17A, and IL8 on the proliferation and melanin synthesis of MCs.
METHODS
Skin specimens were biopsied from patients with psoriasis vulgaris at the active stage, or from the tail skin of Dct-LacZ mice with imiquimod (IMQ)-induced psoriasiform dermatitis. Cultured keratinocytes (KCs), MCs, and human skin explants were used in this study. The numbers of MCs were measured via β-galactosidase staining, EdU incorporation and HMB45 immunohistochemical staining. The expression of human β-defensin 3 (hBD3) in KCs was silenced by siRNA, the conditioned medium (CM) from siRNA-transfected KCs was used to treat MCs, then followed by αMSH stimulation. The melanogenesis-related genes were examined by using qRT-PCR and western blotting.
RESULTS
The increased number of MCs and decreased melanin content were highly relevant to the enhanced expression of IL8 and BD3 both in human psoriatic skin and in IMQ-treated mouse tail skin. IL8 expression in KCs and CXCR2 expression in MCs was significantly increased by IL17A and TNFα, the αMSH-induced upregulations of microphthalmia-associated transcription factor (MITF) and tyrosinase in MCs were abrogated by the CM from hBD3-unsilenced KCs, but not from hBD3-silenced KCs.
CONCLUSION
Our results suggest the roles of IL8-CXCR2 activation in promoting MC proliferation and of BD3 upregulation in reducing melanogenesis. These findings have been implicated in the underlying mechanism that active psoriasis prefers hypopigmentation despite chronic inflammation.
Topics: Humans; Animals; Mice; Tumor Necrosis Factor-alpha; Melanins; Cytokines; Interleukin-8; Melanocytes; Psoriasis; RNA, Small Interfering; Imiquimod; Cell Proliferation; Microphthalmia-Associated Transcription Factor
PubMed: 36577564
DOI: 10.1016/j.jdermsci.2022.11.005 -
Case Reports in Dermatological Medicine 2022Psoriasis is a chronic inflammatory papulosquamous disorder which affects around 2% of the world's population. A peak exacerbation in psoriatic symptoms was noted during...
Psoriasis is a chronic inflammatory papulosquamous disorder which affects around 2% of the world's population. A peak exacerbation in psoriatic symptoms was noted during COVID-19 due to lack of access to dermatological care mixed with heightened emotional stress during the pandemic. This case report describes a 52-year-old admitted male patient who sustained a diffuse rash on multiple areas of his body a week prior to testing positive for COVID-19. We explore plausible causes for the occurrence of the rash, discuss our treatment plan, include relevant clinical pictures, and review published literature to examine conditions that present similarly to the rash seen in our patient. It is crucial for dermatologists to be able to discern various systemic manifestations associated with cutaneous lesions, such as the one seen in this patient, in order to make an accurate and prompt diagnosis. A better understanding of the association between COVID-19 infection and psoriasiform lesions is needed for improving the prognostic and therapeutic outcomes in patients.
PubMed: 36567752
DOI: 10.1155/2022/1820673 -
Schweizer Archiv Fur Tierheilkunde Jan 2023Cyclosporine is a potent immunosuppressive agent used in veterinary medicine to treat a variety of inflammatory or immune mediated conditions. Many adverse effects are...
Cyclosporine is a potent immunosuppressive agent used in veterinary medicine to treat a variety of inflammatory or immune mediated conditions. Many adverse effects are associated with this medication, however most of them rarely occur. A 5-year-old, female intact French bulldog was presented with multiple, multifocally distributed, severe hyperkeratotic and papillomatous/verrucous plaques. The dog was on long-term immunosuppressive treatment with cyclosporine for meningoencephalitis of unknown origin (MUO). It had an history of atopic dermatitis and calcinosis cutis. A papillomavirus infection was excluded by polymerase chain reaction (PCR), and histopathologic analysis revealed a chronic lymphoplasmacytic non-specific dermatitis, perifolliculitis and periadnexitis and focal folliculitis with papillomatous epidermal hyperplasia and orthokeratotic hyperkeratosis. The diagnosis of "cyclosporine-induced epidermal hyperplasia with secondary pyoderma" was made. Cyclosporine was discontinued and as an alternative mycophenolate mofetil was started to control the MUO. An antimicrobial treatment was prescribed for three weeks. After four months, the skin lesions had healed completely. To date after 2 years, the dog is still in remission. The occurrence of hyperplastic lesions associated with cyclosporine therapy have already been described in previous reports. Most of them resemble those of psoriasiform lichenoid dermatitis, although papilloma virus may be detected in some instances. The dog of the present case showed some peculiarities in the histopathological findings, and a papillomavirus involvement was ruled out with PCR. Like observed in a previous report, there was no correlation between cyclosporine blood level and the severity of dermatological changes. A discontinuation of cyclosporine resulted in complete healing in 4 months. This case highlights the importance of regular monitoring and follow-ups in patients on immunosuppressive therapy. Even rare side effects should always be considered in these cases.
Topics: Dogs; Female; Animals; Cyclosporine; Hyperplasia; Immunosuppressive Agents; Papilloma; Dermatitis, Atopic; Chronic Disease; Dog Diseases
PubMed: 36562746
DOI: 10.17236/sat00382 -
Life (Basel, Switzerland) Dec 2022Isorhamnetin (IRh), which has a wide range of pharmacological effects, is one of the most significant active components in the fruits of L. and the leaves of L. It...
Isorhamnetin (IRh), which has a wide range of pharmacological effects, is one of the most significant active components in the fruits of L. and the leaves of L. It protects the heart and brain, in addition to possessing anti-tumor, anti-inflammatory, antioxidant, organ protection, and anti-obesity properties. We sought to assess IRh's anti-psoriatic activity, explore its immunomodulatory properties in reducing the severity of psoriatic symptoms, and evaluate its potential immunotherapeutic effects. We used IRh to treat imiquimod (IMQ)-induced psoriasis in BALB/C mice and examined the underlying mechanisms. The outcomes demonstrated that IRh reduced epidermal hyperplasia, lowered PASI scores, and improved histopathological psoriasiform lesions in IMQ-induced mice. IRh attenuated the accumulation of malondialdehyde (MDA), and also reversed the reduction caused by IMQ of superoxide dismutase (SOD) and catalase (CAT) in skin tissues. Additionally, IRh effectively inhibited IMQ's ability to increase proinflammatory cytokines such as TNF-α, IL-6, IL-17A, and transcription factor NF-κB. Furthermore, IRh significantly reduced the percentage of Th1 and Th17 in the spleens of mice treated with IMQ and suppressed the maturation of splenic dendritic cells. Overall, our research suggests that IRh protects against oxidative stress and inflammation in the pathogenesis of psoriasis, with potential for the development of new and potent medication for the treatment of psoriasis.
PubMed: 36556472
DOI: 10.3390/life12122107 -
Diagnostics (Basel, Switzerland) Dec 2022Palmoplantar psoriasis (PP) is a relatively uncommon variant of psoriasis that affects palms and soles, and that frequently shares both clinical and histologic features...
Palmoplantar psoriasis (PP) is a relatively uncommon variant of psoriasis that affects palms and soles, and that frequently shares both clinical and histologic features with chronic eczema, hyperkeratotic hand dermatitis and allergic contact dermatitis. The present study aims to characterize the histologic features of PP on a series of 21 cases. The following morphological features and their distribution were included: parakeratosis, dilated vessels in papillary dermis, psoriasiform acanthosis with elongation of rete ridges, perivascular lymphocytic infiltrate, decrease/loss of granular layer, Munro's microabscesses, spongiform pustules of Kogoj, spongiosis and lymphocytic exocytosis. The main diagnostic clues and histologic differential diagnoses are also discussed.
PubMed: 36553078
DOI: 10.3390/diagnostics12123071