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Biological & Pharmaceutical Bulletin Oct 2023Psoriasis is classically regarded as a T-helper 1 (Th1) response-dominant disease believed to be antagonized by the Th2 response, which is responsible for allergic...
Psoriasis is classically regarded as a T-helper 1 (Th1) response-dominant disease believed to be antagonized by the Th2 response, which is responsible for allergic diseases, such as atopic dermatitis. The roles of these responses in psoriasis and the relationship between psoriasis and atopic dermatitis have received increasing attention because it is estimated that more than one million patients are concomitantly affected by psoriasis and atopic dermatitis. To address this, we attempted to determine the characteristics of imiquimod-induced psoriasiform lesions in mice with a concomitant allergic response after co-application of the unrelated allergen ovalbumin onto the skin. Imiquimod cream containing ovalbumin was successively applied to the right back skin of hairless HR female mice. Psoriasiform scores were determined for 11 d, and then, the resected skin thickness, spleen weight, and serum antibody levels were examined. In some experiments, mice were allowed free access to ovalbumin-containing water for 10 d before skin application to induce oral tolerance. Imiquimod cream induced psoriasis, and its severity increased upon simultaneous ovalbumin treatment. Increases in anti-ovalbumin immunoglobulin G2a (IgG2a) levels, a Th1 response indicator, and IgG1 and IgE levels, Th2 response indicators, were mediated by ovalbumin addition. Oral tolerance against ovalbumin effectively decreased ovalbumin-exacerbated imiquimod-induced psoriasis, in parallel with a decrease in levels of anti-ovalbumin antibodies. These results suggest that the concomitant allergic response induced by ovalbumin application exacerbates imiquimod-induced psoriasis. This implies that allergic responses to unrelated allergens might exacerbate psoriasis in humans and that modulating such responses could be an effective new approach to treat psoriasis.
PubMed: 37599076
DOI: 10.1248/bpb.b23-00353 -
Clinical, Cosmetic and Investigational... 2023As a mediator of inflammation resolution, lipoxin A4 (LXA4) mainly plays an anti-inflammatory role and promotes inflammation resolution. LXA4 plays an inhibiting...
INTRODUCTION
As a mediator of inflammation resolution, lipoxin A4 (LXA4) mainly plays an anti-inflammatory role and promotes inflammation resolution. LXA4 plays an inhibiting inflammatory role in a variety of diseases, tissues and cells, including keratinocytes. Psoriasis is a chronic inflammatory skin disease mediated by dysregulation of inflammation of immune cells and keratinocytes. However, the expression and role of LXA4 in psoriasis-like mouse models are still unclear.
METHODS
Imiquimod (IMQ) topical treatment of dorsal skin induces psoriasis-like dermatitis in BALB/c mice, pretreated intraperitoneally with or without LXA4 prior to IMQ application. Severity of dorsal lesions is assessed by using a modified human scoring system and histopathology. The concentration of LXA4 and the expression of ALOX15 (a key gene in LXA4 metabolic synthesis) in lesional skins were detected by ELISA and Western blot. Quantitative PCR and ELISA were conducted to detect the mRNA and secretion levels of inflammatory cytokines. The proportion of IL-17A-producing γδT cells in skin and skin draining cervical lymph nodes and helper (Th) 17 cells in spleens was evaluated by flow cytometry. Western blotting was used to analyze the expressions of p-STAT3 and TRAF6.
RESULTS
The concentration of LXA4 and the expression of ALOX15 were decreased in IMQ-induced lesional skin. LXA4 significantly relieved psoriasis-like lesions in IMQ-induced mouse models. Furthermore, LXA4 decreased IMQ-induced systemic inflammation, including reduced the proportion of IL-17A-producing gdT cells in skin and skin draining cervical lymph nodes and Th17 cells in spleens, the secretion and expression of CCL20, IL-17A, IL-1β, and TNF-α in skin and serum. LXA4 markedly inhibited IMQ-induced expression of TRAF6 and p-STAT3.
CONCLUSION
LXA4 significantly ameliorates IMQ-induced psoriasis-like inflammation, and LXA4 can be used as a target for psoriasis treatment.
PubMed: 37575152
DOI: 10.2147/CCID.S418467 -
JAAD Case Reports Sep 2023
PubMed: 37560139
DOI: 10.1016/j.jdcr.2023.06.020 -
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 -
PeerJ 2023Psoriasis is an autoimmune skin disease characterized by immunocyte activation, excessive proliferation, and abnormal differentiation of keratinocytes. Signal...
BACKGROUND
Psoriasis is an autoimmune skin disease characterized by immunocyte activation, excessive proliferation, and abnormal differentiation of keratinocytes. Signal transducers and activators of transcription 3 (STAT3) play a crucial role in linking activated keratinocytes and immunocytes during psoriasis development. T helper (Th) 17 cells and secreted interleukin (IL)-17A contribute to its pathogenesis. IL-17A treated STAT3 overexpressing mouse model might serve as an animal model for psoriasis.
METHODS
In this study, we established a mouse model of psoriasiform dermatitis by intradermal IL-17A injection in STAT3 overexpressing mice. Transcriptome analyses were performed on the skin of wild type (WT), STAT3, and IL-17A treated STAT3 mice. Bioinformatics-based functional enrichment analysis was conducted to predict biological pathways. Meanwhile, the morphological and pathological features of skin lesions were observed, and the DEGs were verified by qPCR.
RESULTS
IL-17A treated STAT3 mice skin lesions displayed the pathological features of hyperkeratosis and parakeratosis. The DEGs between IL-17A treated STAT3 mice and WT mice were highly consistent with those observed in psoriasis patients, including S100A8, S100A9, Sprr2, and LCE. Gene ontology (GO) analysis of the core DEGs revealed a robust immune response, chemotaxis, and cornified envelope, et al. The major KEGG enrichment pathways included IL-17 and Toll-like receptor signaling pathways.
CONCLUSION
IL-17A exacerbates psoriasis dermatitis in a STAT3 overexpressing mouse.
Topics: Mice; Animals; Interleukin-17; Imiquimod; Psoriasis; Skin; Disease Models, Animal; Dermatitis
PubMed: 37465147
DOI: 10.7717/peerj.15727 -
Actas Dermo-sifiliograficas Jan 2024Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been... (Review)
Review
BACKGROUND
Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions.
MATERIAL AND METHODS
Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain.
RESULTS
We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution.
CONCLUSIONS
Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.
Topics: Humans; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor Inhibitors; Adalimumab; Infliximab; Psoriasis; Immunologic Factors; Necrosis
PubMed: 37437689
DOI: 10.1016/j.ad.2023.06.016 -
Clinical, Cosmetic and Investigational... 2023Pretibial pruritic papular dermatitis (PPPD) is a distinctive skin disorder in response to persistent pretibial manipulation. Clinically, it manifests as multiple...
Pretibial pruritic papular dermatitis (PPPD) is a distinctive skin disorder in response to persistent pretibial manipulation. Clinically, it manifests as multiple discrete, pruritic, flesh-colored-to-erythematous papules and plaques confined to the pretibial area. The histological hallmark of PPPD comprises irregular epidermal psoriasiform hyperplasia with parakeratosis and spongiosis, dermal fibrosis, and lymphohistiocytic infiltration. Due to its rarity and underrecognition, the prevalence and standard treatment of the disease have yet to be well elucidated. Here, we present a case of PPPD in a 60-year-old female presenting with numerous pruritic, erythematous-to-brownish papules and plaques on bilateral pretibial areas for 1.5 years. The lesions were significantly improved after 1 month of additional treatment with oral pentoxifylline. In this report, we aim to raise awareness in recognizing PPPD since it manifests unique clinical, dermoscopic, and histological features, representing pretibial skin's response to chronic rubbing. In addition, we proposed a novel effective therapy for the disease using pentoxifylline.
PubMed: 37366429
DOI: 10.2147/CCID.S420726 -
Biologics-Induced Immunophenotypic Cross-Switching in Patients with Psoriasis and Atopic Dermatitis.Indian Journal of Dermatology 2023Antibody-based therapies that inhibit pro-inflammatory cytokine signalling are commonly used in dermatology. Paradoxically, these biological agents may induce or... (Review)
Review
Antibody-based therapies that inhibit pro-inflammatory cytokine signalling are commonly used in dermatology. Paradoxically, these biological agents may induce or exacerbate paradoxical reactions. Recently, it has been reported that the treatment of eczema with dupilumab can lead to the development of psoriasiform eruptions, which we called psoriasiform paradoxical reactions (P-PRs). Conversely, cases of eczematous paradoxical reactions (E-PRs) have also been described in patients with psoriasis treated with biologics. To summarise the case characteristics and disease features of phenotypic transition between psoriasis and eczematoid dermatitis, and to explore the mechanism or connection related to biological agents or patients' genetic characteristics, a systematic review was conducted for P-PRs in atopic dermatitis and E-PRs in patients with psoriasis treated with corresponding biological agents, respectively. We identified a series of P-PRs in 42 atopic dermatitis cases treated with dupilumab. The time to onset of P-PRs typically ranged from weeks to months, with a mean latency period of 22.65 weeks. Almost all patients presented with new-onset P-PRs. Simultaneously, we reviewed 22 articles reporting 51 patients with psoriasis with biological agent-induced E-PRs, which occurred on average at 24.47 weeks, 72.55% of them induced by IL-17A inhibitors. 48.98% (24/49) of cases reported a positive personal history of atopy, which may suggest an increased risk of biological agent-induced paradoxical eruptions. Overall, the improvement or resolution upon discontinuation of the inciting biologics was relatively common, and further studies are needed to estimate the real prevalence and unveil the pathophysiological mechanisms of these paradoxical events.
PubMed: 37275804
DOI: 10.4103/ijd.ijd_871_22 -
Journal of Inflammation Research 2023Psoriasis is a recurring systemic disease that can be treated with biologics to some effect. However, precisely targeting inflammatory mediators may disrupt immune...
Psoriasis is a recurring systemic disease that can be treated with biologics to some effect. However, precisely targeting inflammatory mediators may disrupt immune system homeostasis and lead to new conditions. Here, we report a case of psoriasiform dermatitis (PsoD) caused by IL-17 inhibitors (IL-17i) namely secukinumab treatment for psoriasis. This case proposes an effective use of Janus kinase inhibitor (JAKi) tofacitinib to confront lesions induced by IL-17i. This is the first case report of PsoD caused by secukinumab treated with tofacitinib.
PubMed: 37228572
DOI: 10.2147/JIR.S412418 -
International Journal of Nanomedicine 2023[This corrects the article DOI: 10.2147/IJN.S165966.].
Erratum: Chitosan-Based Nanoformulated (-)-Epigallocatechin-3-Gallate (EGCG) Modulates Human Keratinocyte-Induced Responses and Alleviates Imiquimod-Induced Murine Psoriasiform Dermatitis [Erratum].
[This corrects the article DOI: 10.2147/IJN.S165966.].
PubMed: 37197027
DOI: 10.2147/IJN.S416060