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Immunity, Inflammation and Disease Jul 2023A recent study confirmed that thiolutin (THL), as a potent inflammasome inhibitor, plays a promising therapeutic role in multiple inflammatory disease models. However,...
INTRODUCTION
A recent study confirmed that thiolutin (THL), as a potent inflammasome inhibitor, plays a promising therapeutic role in multiple inflammatory disease models. However, the effect of THL on psoriasis has not been reported so far.
METHODS
A psoriasiform dermatitis model was prepared by applying 5% imiquimod (IMQ) cream on mice. A total of 36 mice were randomly divided into six groups: control, model, model + THL-L/M/H (THL, 1/2.5/5 mg/kg/day), model + methotrexate (1 mg/kg/day). Psoriasis area and severity index (PASI) scores were observed and calculated. The histological changes in skin, liver, and kidney tissues were observed by hematoxylin and eosin staining. Alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and blood creatinine were measured by automatic biochemistry analyzer. The size of the spleens was determined, and the proportion of Foxp3 + CD4+ regulatory T (Treg) cells in the spleens was tested by flow cytometry. The proinflammatory factors and nucleotide oligomerization domain nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome protein levels were examined by reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and immunohistochemistry, respectively.
RESULTS
THL administration preeminently reduced the thickness, scaling, and erythema of the skin lesions, alleviated IMQ-induced psoriasiform lesions in mice, reduced the PASI score, and ameliorated histopathological changes in mouse skin. The spleen index was decreased by almost half and the proportion of Foxp3 + CD4+ Treg cells was increased after intervention by THL. THL intervention did not affect liver and kidney function, but decreased the expression levels of proinflammatory factors and NLRP3 inflammasome in the skin of psoriatic mice.
CONCLUSIONS
THL may alleviate IMQ-induced psoriasis-like manifestations in mice by inhibiting NLRP3 inflammasome.
Topics: Mice; Animals; Imiquimod; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Psoriasis; Dermatitis; Inflammation; Forkhead Transcription Factors
PubMed: 37506136
DOI: 10.1002/iid3.877 -
Annals of Dermatology Dec 2020Psoriasis is a common chronic inflammatory skin disease. The development of psoriasis is dependent on many intercellular events such as innate immunity and T...
BACKGROUND
Psoriasis is a common chronic inflammatory skin disease. The development of psoriasis is dependent on many intercellular events such as innate immunity and T cell-mediated inflammation. Furthermore, genetic factors are strongly implicated in the pathophysiology of psoriasis. Although a variety of susceptible genes are identified, it is likely that many important genes remain undisclosed.
OBJECTIVE
The aim of this study is to investigate the possible role of lysine demethylase 2A (KDM2A) in the pathophysiology of psoriasis.
METHODS
We examined the expression of KDM2A using a well established imiquimod-induced psoriasiform dermatitis model.
RESULTS
Immunohistochemistry analysis showed that expression of KDM2A was increased in imiquimod-induced psoriasiform dermatitis. Consistent with this result, KDM2A level was markedly increased in the epidermis of psoriatic patient. When keratinocytes were stimulated with TLR3 agonist poly(I:C), KDM2A was increased at both the mRNA and protein levels. Poly(I:C) increased the expression of psoriasis-related cytokines including tumor necrosis factor-α, interleukin-8, and CCL20, and KDM2A inhibitor daminozide enhanced the poly(I:C)-induced cytokine expression. Finally, topical co-application of imiquimod and daminozide exacerbated the imiquimod-induced psoriasiform dermatitis.
CONCLUSION
Together, these results suggest that KDM2A is increased to negatively regulate the inflammatory reaction of epidermal keratinocytes in psoriasis.
PubMed: 33911791
DOI: 10.5021/ad.2020.32.6.481 -
Biochimica Et Biophysica Acta Mar 2014Deficiency of sterol C4 methyl oxidase, encoded by the SC4MOL gene, has recently been described in four patients from three different families. All of the patients... (Review)
Review
Deficiency of sterol C4 methyl oxidase, encoded by the SC4MOL gene, has recently been described in four patients from three different families. All of the patients presented with microcephaly, congenital cataracts, and growth delay in infancy. The first patient has suffered since the age of six years from severe, diffuse, psoriasiform dermatitis, sparing only her palms. She is now 20 years old. The second patient is a 5 year old girl who has just started to develop dry skin and hair changes. The third and fourth patients are a pair of affected siblings with a severe skin condition since infancy. Quantitative sterol analysis of plasma and skin scales from all four patients showed marked elevation of 4α-methyl- and 4, 4'-dimethylsterols, consistent with a deficiency in the first step of sterol C4 demethylation in cholesterol biosynthesis. Mutations in the SC4MOL have been identified in all of the patients. SC4MOL deficiency is the first autosomal recessive disorder identified in the sterol demethylation complex. Cellular studies with patient-derived fibroblasts have shown a higher mitotic rate than control cells in cholesterol-depleted medium, with increased de novo cholesterol biosynthesis and accumulation of methylsterols. Immunologic analyses of granulocytes and B cells from patients and obligate carriers in the patients' families indicated dysregulation of immune-related receptors. Inhibition of sterol C4 methyl oxidase in human transformed lymphoblasts induced activation of the cell cycle. Additional studies also demonstrated diminished EGFR signaling and disrupted vesicular trafficking in cells from the affected patients. These findings suggest that methylsterols play an important role in epidermal biology by their influence on cell proliferation, intracellular signaling, vesicular trafficking and immune response. SC4MOL is situated within the psoriasis susceptibility locus PSORS9, and may be a genetic risk factor for common skin conditions. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.
Topics: Adult; B-Lymphocytes; Cell Proliferation; Child, Preschool; Cholesterol; Dermatitis; Epidermis; Female; Fibroblasts; Genetic Loci; Granulocytes; Humans; Lipid Metabolism, Inborn Errors; Mutation; Oxidoreductases; Signal Transduction
PubMed: 24144731
DOI: 10.1016/j.bbalip.2013.10.009 -
Oncotarget Apr 2016Nijmegen Breakage Syndrome is a disease caused by NBN mutations. Here, we report a novel function of Nbn in skin homeostasis. We found that Nbn deficiency in hair...
Nijmegen Breakage Syndrome is a disease caused by NBN mutations. Here, we report a novel function of Nbn in skin homeostasis. We found that Nbn deficiency in hair follicle (HF) progenitors promoted increased DNA damage signaling, stimulating p16Ink4a up-regulation, Trp53 stabilization and cytokines secretion leading to HF-growth arrest and hair loss. At later stages, the basal keratinocytes layer exhibited also enhanced DNA damage response but in contrast to the one in HF progenitor was not associated with pro-inflammatory cytokines expression, but rather increased proliferation, lack of differentiation and immune response resembling psoriasiform dermatitis. Simultaneous Nbn and Trp53 inactivation significantly exacerbated this phenotype, due to the lack of inhibition of pro-inflammatory cytokines secretion by Trp53. Altogether, we demonstrated novel functions of Nbn in HF maintenance and prevention of skin inflammation and we provide a mechanistic explanation that links cell intrinsic DNA maintenance with large scale morphological tissue alterations.
Topics: Alopecia; Animals; Cell Cycle Proteins; DNA-Binding Proteins; Dermatitis; Epidermis; Mice; Mice, Knockout; Nuclear Proteins; Phenotype; Psoriasis; Tumor Suppressor Protein p53
PubMed: 27050272
DOI: 10.18632/oncotarget.8470 -
Medicina (Kaunas, Lithuania) Feb 2024: New oncologic therapies, including immune checkpoint inhibitors (ICIs), have revolutionized the survival and prognosis of cancer patients. However, these therapies are... (Review)
Review
: New oncologic therapies, including immune checkpoint inhibitors (ICIs), have revolutionized the survival and prognosis of cancer patients. However, these therapies are often complicated by immune-related adverse effects (irAEs) that may impact quality of life and potentially limit their use. Among these adverse events are psoriasis and psoriatic arthritis that may develop de novo or flare under treatment with ICIs. Given the exceptional immune status of patients receiving ICIs, managing these conditions without interfering with the effect of the oncologic treatment may prove very challenging. Aim: To review the literature data on ICI-induced psoriasis exacerbation or development, to present our own experience, and to discuss the pathogenic mechanisms underlying this association and the optimal therapeutic approach for these patients. Case Reports: We report three cases of ICI-induced de novo psoriasis and two cases of ICI-induced psoriasis exacerbation that required systemic treatment. Oral acitretin treatment successfully controlled psoriasis lesions in three cases and allowed for the continuation of immunotherapy. : We performed a medical literature search across several databases (PubMed, Medline, Google Scholar) using the search terms "immune checkpoint inhibitor-induced psoriasis/psoriasiform dermatitis/psoriasis arthritis". We identified and revised 80 relevant publications that reported 1102 patients with psoriasis and/or psoriasis arthritis induced or exacerbated by ICIs. We assessed the type of cancer, the therapeutic agent involved, the clinical form of psoriasis, the presence or absence of psoriatic arthritis, the personal and family history of psoriasis, the age, the gender, the time until onset or exacerbation of skin lesions, the specific treatment recommended, the need for ICI discontinuation, and the patient's outcome. : As ICIs represent a fairly novel therapy, the association with several adverse effects is only now unraveling. Psoriasis exacerbation or onset following the initiation of immunotherapy is one such example, as more and more reports and case series are being published. Awareness of the relationship between psoriasis and treatment with ICIs, prompt recognition, and initiation of adequate skin-directed therapies are essential for the avoidance of skin lesions worsening, the need for systemic treatments that may interfere with ICIs' effects, or the discontinuation of the latter. In the absence of generally accepted guidelines, it is advisable to treat patients with severe, widespread psoriasis with drugs that do not impair the effects of immunotherapy and thus do not alter the patient's prognosis.
Topics: Humans; Immune Checkpoint Inhibitors; Arthritis, Psoriatic; Quality of Life; Psoriasis; Neoplasms
PubMed: 38541099
DOI: 10.3390/medicina60030373 -
Journal of Clinical and Investigative... Jul 2023Seborrheic dermatitis (SD) is an inflammatory disease that has a papulosquamous morphology in areas rich in sebaceous glands such as the scalp, face, and body folds....
BACKGROUND
Seborrheic dermatitis (SD) is an inflammatory disease that has a papulosquamous morphology in areas rich in sebaceous glands such as the scalp, face, and body folds. Petaloid SD is an uncommon presentation found in patients with dark skin (Fitzpatrick Skin type V-VI). This form of SD can appear as pink or hypopigmented polycyclic coalescing rings or scaly macules and patches in the typical areas SD appears, which can mimic other conditions including lupus erythematosus. There is significant disproportion in the representation of darker skin types in dermatological textbooks and scarce literature on petaloid SD. This case demonstrates the presentation of the petaloid SD in an African American patient to contribute to the limited literature on dermatological conditions within this population.
CASE REPORT
A 25-year-old African American female with a history of mild hidradenitis suppurativa and asthma who presented with asymptomatic hypopigmented rashes throughout her face, scalp, and chest. She was diagnosed with the petaloid form SD and treated with ketoconazole shampoo once weekly, ketoconazole cream 1-2x daily, and hydrocortisone 2.5% ointment twice daily as needed. At six-week post-treatment follow-up, the patient's rashes significantly improved.
CONCLUSIONS
The petaloid form of SD is commonly experienced in dark-skinned patients. While common treatments for SD are effective in this form of SD, special consideration of skin types, skincare habits, and haircare in the African American population should be explored. This case report demonstrates how this uncommon skin condition presents in patients of Fitzpatrick skin type V-VI and a successful treatment course.
PubMed: 38249156
DOI: 10.13188/2373-1044.1000086 -
Frontiers in Medicine 2021Superficial perivascular dermatitis, an important type of inflammatory dermatosis, comprises various skin diseases, which are difficult to distinguish by clinical...
Superficial perivascular dermatitis, an important type of inflammatory dermatosis, comprises various skin diseases, which are difficult to distinguish by clinical manifestations and need pathological imaging observation. Coupled with its complex pathological characteristics, the subtype classification depends to a great extent on dermatopathologists. There is an urgent need to develop an efficient approach to recognize the pathological characteristics and classify the subtypes of superficial perivascular dermatitis. 3,954 pathological images (4 × and 10 ×) of three subtypes-psoriasiform, spongiotic and interface-of superficial perivascular dermatitis were captured from 327 cases diagnosed both clinically and pathologically. The control group comprised 1,337 pathological images of 85 normal skin tissue slides taken from the edge of benign epidermal cysts. First, senior dermatologists and dermatopathologists followed the structure-pattern analysis method to label the pathological characteristics that significantly contribute to classifying different subtypes on 4 × and 10 × images. A cascaded deep learning algorithm framework was then proposed to establish pixel-level pathological characteristics' masks and classify the subtypes by supervised learning. 13 different pathological characteristics were recognized, and the accuracy of subtype classification was 85.24%. In contrast, the accuracy of the subtype classification model without recognition was 71.35%. Our cascaded deep learning model used small samples to deliver efficient recognition of pathological characteristics and subtype classification simultaneously. Moreover, the proposed method could be applied to both microscopic images and digital scanned images.
PubMed: 34336900
DOI: 10.3389/fmed.2021.696305 -
The Journal of Investigative Dermatology Jun 2019
Topics: Animals; Diet, Carbohydrate-Restricted; Diet, High-Fat; Diet, Western; Dietary Sugars; Disease Models, Animal; Disease Susceptibility; Female; Humans; Imiquimod; Mice; Obesity; Psoriasis
PubMed: 30571973
DOI: 10.1016/j.jid.2018.12.002 -
Annals of Dermatology Apr 2020
Psoriasiform Dermatitis Related with T-Cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Motif Domains Inhibitor in a Patient with Non-Small-Cell Lung Cancer.
PubMed: 33911733
DOI: 10.5021/ad.2020.32.2.172 -
The American Journal of Pathology Jul 2003Itgb2(tm1Bay) PL/J mice express low levels of the beta(2) integrins and, unlike Itgb2(tm1Bay) C57BL/6J mice, spontaneously develop psoriasiform dermatitis with several...
Itgb2(tm1Bay) PL/J mice express low levels of the beta(2) integrins and, unlike Itgb2(tm1Bay) C57BL/6J mice, spontaneously develop psoriasiform dermatitis with several similarities to human psoriasis. To define the genetic requirements for skin disease susceptibility we analyzed more than 500 F2 progeny from an Itgb2(tm1Bay) (PL/J x C57BL/6J) intercross. We found that 23.5% developed chronic inflammatory skin disease, although significant differences in severity were observed. Another CD18 mutation, Itgb2(tm2Bay), has now been generated that completely eliminates CD18 expression. Surprisingly, of 10 Itgb2(tm2Bay) homozygote PL/J N4 mice generated, none showed clinical or histopathological evidence of disease. However, Itgb2(tm1Bay)/Itgb2(tm2Bay) PL/J mice developed dermatitis indistinguishable from Itgb2(tm1Bay) PL/J mice. In addition, approximately half of Itgb2(tm1Bay)/Itgb2(tm2Bay) (C57BL/6J x PL/J)F1 mice were found to develop mild psoriasiform dermatitis identical to the early stages of disease seen in Itgb2(tm1Bay) PL/J mice. Collectively, these results suggest a complex inheritance pattern of psoriasiform dermatitis in this model that involves lowered, but not absent, CD18 expression and at least two additional PL/J loci for the development of severe disease. The susceptibility allele can act in either a heterozygous or homozygous state, dependent on the level of CD18 expression.
Topics: Animals; CD18 Antigens; Dermatitis; Disease Models, Animal; Disease Progression; Humans; Mice; Mice, Inbred Strains; Mutation; Psoriasis; Skin
PubMed: 12819024
DOI: 10.1016/S0002-9440(10)63643-7