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Theranostics 2024Macrophage-associated inflammation and keratinocytes excessive proliferation and inflammatory cytokines secretion induced by stimulation play an important role in the...
Macrophage-associated inflammation and keratinocytes excessive proliferation and inflammatory cytokines secretion induced by stimulation play an important role in the progression of psoriasiform dermatitis. However, how these two types of cells communicate remains obscure. We induced a mouse model with experimental psoriasiform dermatitis by Imiquimod (IMQ). To investigate whether damaged keratinocytes promote macrophage polarization and accelerate skin lesions by releasing extracellular vesicle (EV), purified EV were isolated from the primary epidermis of 5-day IMQ-induced psoriasiform dermatitis model mice, and then fluorescence-labeled the EV with PKH67. The EV was injected into the skin of mice treated with IMQ or vehicle 2 days . In addition, we established a co-culture system of the human monocytic cell line (THP-1) and HaCaT, and THP-1/HaCaT conditioned media culture model respectively. Subsequently, we evaluated the effect of Leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EV on macrophage activation. We demonstrated macrophages can significantly promote keratinocyte inflammation and macrophage polarization may be mediated by intercellular communication with keratinocytes. Interestingly, IMQ-induced 5-day, keratinocyte-derived EV recruited macrophage and enhanced the progression of skin lesions. Similar to results , EV released from M5-treated HaCaT significantly promotes Interleukin 1β (IL-1β) and Tumor necrosis factor α (TNF-α) expression of THP-1 cells. Importantly, we found that LRG1-enriched EV regulates macrophages via TGF beta Receptor 1 (TGFβR1) dependent process. Our findings indicated a novel mechanism for promoting psoriasiform dermatitis, which could be a potential therapeutic target.
Topics: Humans; Animals; Mice; Keratinocytes; Macrophages; Extracellular Vesicles; Glycoproteins; Inflammation; Dermatitis
PubMed: 38250043
DOI: 10.7150/thno.89180 -
Frontiers in Pharmacology 2022Cannabinoid receptor 2 (CB2R) is a potential target for anti-inflammatory and pain therapeutics given its significant immunomodulatory and analgesic effects. However,...
Cannabinoid receptor 2 (CB2R) is a potential target for anti-inflammatory and pain therapeutics given its significant immunomodulatory and analgesic effects. However, the role of CB2R in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) and itch is poorly understood. To investigate the function and mechanism of CB2R in PsD and itch in mice. Following daily treatment with topical IMQ cream for 5-7 consecutive days in C56BL/6 wild-type (WT) and CB2R gene knockout (KO) mice, we assessed the Psoriasis Area and Severity Index (PASI) scores and the scratch bouts every day, and hematoxylin and eosin (H&E) staining, toluidine blue staining were used to observe the histological changes. mRNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels were detected by western blotting (WB), immunohistochemistry (IHC), immunofluorescence (IF) and cytometric bead array (CBA). Flow cytometry (FCM) was used to examine the proportion of Th17/Treg cells. We found that CB2R expression levels were increased in mice with psoriasis. Compared with WT mice, CB2R deficiency exacerbated IMQ-induced PsD and scratching bouts and upregulated the expression of proinflammatory cytokines by increasing the infiltration of CD4 T cells and the Th17/Treg ratio. Obvious proliferation and prolongation of nerve fibers and high expression of nerve growth factor (NGF) were observed in PsD and CB2R KO mice. Pretreatment with the CB2R agonist, JWH-133 significantly reversed inflammation and scratching bouts. CB2R didn't participate in the induction of itch in psoriasis by regulating the expression of IL-31, thymic stromal lymphopoietin (TSLP) and mast cells in mouse skins. Our results demonstrate that CB2R plays a pivotal role in the pathophysiology of psoriasis, providing a new potential target for anti-inflammatory and antipruritic drugs.
PubMed: 35173615
DOI: 10.3389/fphar.2022.790712 -
The Journal of Dermatological Treatment Dec 2023Atopic dermatitis (AD), a chronic-relapsing inflammatory skin disorder, manifests with intense itching and eczematous lesions impairing quality of life. A heterogeneous... (Review)
Review
Atopic dermatitis (AD), a chronic-relapsing inflammatory skin disorder, manifests with intense itching and eczematous lesions impairing quality of life. A heterogeneous population, and regional clinical practices for treating AD warrant the development of guidelines in Qatar. Therefore, guidelines for the management of moderate-to-severe AD in Qatar have been developed and discussed. Experts, including dermatologists and immunologists, used the Delphi technique for developing guidelines. Consensus was defined as ≥75% agreement or disagreement. AD is highly prevalent in primary and tertiary dermatology centers. AD-associated foot eczema and psoriasiform eczema are more frequent in Qatar than in Europe or USA. SCORing Atopic Dermatitis Index quantifies disease severity and itch. Dermatology Life Quality Index assesses the quality of life. Atopic Dermatitis Control Tool assesses long-term disease control. Moderate-severe AD benefits from new topicals like Janus-kinase-inhibitors or PDE4-inhibitors combined with phototherapy. Currently approved systemic agents are dupilumab, baricitinib, abrocitinib, and upadacitinib. New anti-IL-13 and anti-IL-31 therapies will soon be available. Patient education, allergy testing, and comorbidity consideration are critical in the management of AD. The expert panel established a comprehensive and pragmatic approach to managing moderate-to-severe AD, thereby assisting clinical decision-making for healthcare professionals in Qatar.
Topics: Humans; Dermatitis, Atopic; Expert Testimony; Qatar; Quality of Life; Eczema; Pruritus
PubMed: 37700510
DOI: 10.1080/09546634.2023.2251622 -
Pediatric Dermatology Nov 2021Psoriasiform eruptions after initiation of dupilumab have been previously described in adults. This report details the risk of developing or unmasking psoriasiform...
BACKGROUND/OBJECTIVES
Psoriasiform eruptions after initiation of dupilumab have been previously described in adults. This report details the risk of developing or unmasking psoriasiform eruptions after initiation of dupilumab in children.
METHODS
Records of patients ≤18 years of age with atopic dermatitis who developed psoriasiform dermatitis during treatment with dupilumab were reviewed retrospectively.
RESULTS
Six children, 4-18 years of age, on dupilumab for severe atopic dermatitis developed new-onset psoriasiform dermatitis at a median duration of 8 months (range, 6-12 months) after dupilumab initiation. Typical locations of psoriasis were involved (face, scalp, trunk, and extensor extremities). The majority showed clearance or near clearance with the use of medium-strength to potent topical corticosteroid ointments and 83% continued use of the dupilumab. A 7th patient had psoriasis, in addition to severe atopic dermatitis, and the psoriasis was unmasked by its failure to respond to dupilumab.
CONCLUSION
Although unusual, psoriasiform lesions can appear during effective treatment with dupilumab for atopic dermatitis, potentially reflecting a shift toward cutaneous IL-23/T 17 pathway activation with dupilumab-induced suppression of type 2 immunity.
Topics: Adult; Antibodies, Monoclonal, Humanized; Child; Dermatitis, Atopic; Eczema; Humans; Retrospective Studies
PubMed: 34647354
DOI: 10.1111/pde.14820 -
Actas Dermo-sifiliograficas Oct 2016In vivo reflectance confocal microscopy (RCM) is a relatively novel non-invasive tool for microscopic evaluation of the skin used prevalently for diagnosis and... (Review)
Review
In vivo reflectance confocal microscopy (RCM) is a relatively novel non-invasive tool for microscopic evaluation of the skin used prevalently for diagnosis and management of skin tumour. Its axial resolution, its non-invasive and easy clinical application represents the goals for a large diffusion of this technique. During the last 15 years, RCM has been demonstrated to be able to increase the sensibility and sensitivity of dermoscopy in the diagnosis of skin tumours integrating in real time clinic, dermoscopic and microscopic information useful for the definition of malignancy. Despite to date, no large comparative studies on inflammatory skin diseases has been published in the literature, several papers already showed that RCM has a potential for the evaluation of the descriptive features of the most common inflammatory skin diseases as psoriasis, lupus erythematosus, contact dermatitis and others. The aim of the application of this technique in non-neoplastic skin diseases has been prevalently focused on the possibility of clinical diagnosis confirmation, as well as therapeutic management. Moreover, the use of RCM as driver for an optimised skin biopsy has been also followed in order to reduce the number of unsuccessful histopathological examination. In this review article we describe the confocal features of the major groups of inflammatory skin disorders focusing on psoriasiform dermatitis, interface dermatitis and spongiotic dermatitis.
Topics: Dermatitis; Dermoscopy; Diagnosis, Differential; Epidermis; Humans; Microscopy, Confocal; Psoriasis; Sensitivity and Specificity
PubMed: 26996333
DOI: 10.1016/j.ad.2016.01.010 -
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 -
Pediatric and Developmental Pathology :... 2018Inflammatory dermatoses encompass a variety of histologic patterns that affect different portions of the skin. In spongiotic, psoriasiform, lichenoid, pityriasiform, and... (Review)
Review
Inflammatory dermatoses encompass a variety of histologic patterns that affect different portions of the skin. In spongiotic, psoriasiform, lichenoid, pityriasiform, and blistering disorders, there are predominately epidermal and junctional activities with variable superficial dermal inflammation. Hypersensitivity reactions can show either epidermal or mostly dermal changes depending on whether the exposure of the exogenous allergen occurs through an external or internal route, respectively. Exceptions include erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis, where the etiology is often due to infection or ingested medications, but the histologic features are almost exclusively confined to the epidermis and dermoepidermal junction. Autoimmune disorders are unique in that lesions typically incorporate a mixture of epidermal and dermal inflammatory patterns with periadnexal inflammation, while the vast majority of vasculitis/vasculopathy and alopecia have changes limited to only the vessels and hair follicles, respectively. It is critical to recognize that a relatively limited number of histologic patterns are seen in a large array of clinical entities. Therefore, clinicopathologic correlation and careful examination of histologic details are of the utmost importance when evaluating skin biopsies for inflammatory disorders.
Topics: Biopsy; Child; Dermatitis; Humans; Skin
PubMed: 29607753
DOI: 10.1177/1093526617748781 -
Dermatologic Clinics Oct 2016Reflectance confocal microscopy (RCM) allows real-time, noninvasive microscopic view of the skin at nearly histologic resolution serially over time. RCM increases the... (Review)
Review
Reflectance confocal microscopy (RCM) allows real-time, noninvasive microscopic view of the skin at nearly histologic resolution serially over time. RCM increases the sensibility and sensitivity of the diagnosis of skin tumours. RCM evaluates descriptive features of psoriasis, lupus erythematosus, contact dermatitis, and others. Three groups of optical histology have been described: psoriasiform, spongiotic, and interface dermatitis. In a multicenter study, RCM patterns of spongiotic, hyperkeratotic, and interface dermatitis have been analyzed and an algorithmic method of analysis for fast application in the clinical setting based on a multivariate analysis has been proposed. A tree decision diagram has been also established.
Topics: Algorithms; Decision Trees; Dermatitis; Dermatitis, Contact; Hair Diseases; Humans; Intravital Microscopy; Lupus Erythematosus, Cutaneous; Microscopy, Confocal; Psoriasis; Scalp Dermatoses
PubMed: 27692454
DOI: 10.1016/j.det.2016.05.011 -
British Journal of Pharmacology Aug 2023Neutrophilic inflammation is a critical pathogenic factor in psoriasis. The therapeutic applicability of palbociclib, a cyclin-dependent kinase 4 and 6 (CDK4/6)...
BACKGROUND AND PURPOSE
Neutrophilic inflammation is a critical pathogenic factor in psoriasis. The therapeutic applicability of palbociclib, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor clinically used to treat cancer, in the treatment of neutrophil-associated psoriasis remains undefined. In this study, we evaluated the therapeutic potential and pharmacological effect of palbociclib on neutrophil-associated psoriasiform dermatitis.
EXPERIMENTAL APPROACH
The anti-inflammatory effects of palbociclib were determined in activated human neutrophils. The therapeutic feasibility of palbociclib in psoriasis was demonstrated in a mouse model of imiquimod-induced psoriasiform dermatitis. The in vitro enzymatic assays and in silico analyses were used to identify the underlying pharmacological mechanisms.
KEY RESULTS
This study found that palbociclib inhibited neutrophilic inflammation, including superoxide anion generation, reactive oxygen species (ROS) formation, elastase degranulation and chemotactic responses. The mechanistic studies identified that the anti-inflammatory effects of palbociclib involved the targeting of phosphatidylinositol 3-kinase (PI3K) but not CDK4/6 in human neutrophils. Palbociclib preferentially targeted the p110δ catalytic subunit of PI3K and thereby blocked signalling via the PI3K/protein kinase B (Akt) pathway. Furthermore, topical application of palbociclib significantly ameliorated imiquimod-induced psoriasiform dermatitis in mice, including psoriatic symptoms, neutrophil infiltration, Akt activation and cytokine up-regulation.
CONCLUSIONS AND IMPLICATIONS
This is the first study to demonstrate that palbociclib can potentially be used to treat neutrophil-associated psoriasiform dermatitis through the targeting of neutrophilic PI3K activity. Our findings prompt further research to explore the potential of palbociclib and PI3K in psoriasis and other inflammatory diseases.
Topics: Humans; Animals; Mice; Proto-Oncogene Proteins c-akt; Imiquimod; Phosphatidylinositol 3-Kinases; Psoriasis; Inflammation; Dermatitis; Anti-Inflammatory Agents; Disease Models, Animal
PubMed: 36967633
DOI: 10.1111/bph.16080 -
Clinical and Experimental Dermatology Jan 2021While the majority of children with a chronic itchy rash suffer from atopic dermatitis (AD) and other forms of dermatitis, psoriasis is in the differential diagnosis....
BACKGROUND
While the majority of children with a chronic itchy rash suffer from atopic dermatitis (AD) and other forms of dermatitis, psoriasis is in the differential diagnosis. Certain patterns such as guttate and napkin psoriasis are accepted as classic paediatric psoriasis (PP); however, there are many patients who do not fit these classic forms of PP nor fulfil the accepted criteria for AD. 'Psoriasiform dermatitis' (PD) is a term that has been used for these patients; however, it has not been formally defined. Identification of this group of patients, who although not having the typical clinical features of psoriasis, respond well to psoriasis-specific treatment, may assist treatment decisions for these patients.
AIM
To describe PD and compare it with typical PP.
METHODS
Patients with classic PP (n = 109) were compared with a control group with AD (n = 449) and assessed for 21 clinical features associated with PP. Multivariate nonlinear regression analyses determined which features best separated the groups. Patients with dermatitis who demonstrated any of these 21 features (n = 43), which were used to diagnose PD, were then compared with the PP and AD groups. They were managed with psoriasis-specific treatment and Psoriasis Area and Severity Index (PASI) was recorded.
RESULTS
Of the 21 clinical features, 12 were found to clearly separate the classic PP and AD groups. Using the eight most significant (P < 0.0001) features, we found these two groups clearly separated at a score of 3 out of 8. Children with PD with ≥ 4 of these features responded well to treatment for psoriasis with a mean reduction of PASI by 85% at 6 weeks.
CONCLUSIONS
We found that patients with dermatitis who have ≥ 4 psoriasis-associated features may have a condition that has been previously alluded to but not defined in the literature, 'psoriasiform dermatitis'. Treatments usually reserved for patients with psoriasis appear to be effective in these patients.
Topics: Case-Control Studies; Child; Dermatitis; Dermatitis, Atopic; Diagnosis, Differential; Humans; Psoriasis
PubMed: 32735691
DOI: 10.1111/ced.14373