- A Critical Role of the IL-1β-IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis. [Journal Article]
- JIJ Invest Dermatol 2018 Aug 15
- IL-1 signaling pathway has been shown to play a critical role in the pathogenesis of chronic, autoinflammatory skin diseases such as psoriasis. However, the exact cellular and molecular mechanisms ha...
IL-1 signaling pathway has been shown to play a critical role in the pathogenesis of chronic, autoinflammatory skin diseases such as psoriasis. However, the exact cellular and molecular mechanisms have not been fully understood. Here, we show that IL-1β is significantly elevated in psoriatic lesional skin and imiquimod (IMQ)-treated mouse skin. In addition, IL-1R signaling appears to correlate with psoriasis disease progression and treatment response. IL-1 signaling in both dermal γδ T cells and other cells such as keratinocytes is essential to an IMQ-induced skin inflammation. IL-1β induces dermal γδ T cell proliferation and IL-17 production in mice. In addition, IL-1β stimulates keratinocytes to secrete chemokines which preferentially chemoattract peripheral CD27- CCR6+IL-17 capable producing γδ T cells (γδT17). Further studies reveal that endogenous IL-1β secretion is regulated by skin commensals to maintain dermal γδT17 homeostasis in mice. Mouse skin associated with corynebacterium, bacterial enriched in human psoriatic lesional skin has increased IL-1β and dermal γδT17 cell expansion. Thus, IL-1β-IL-1R signaling pathway may contribute to skin inflammation and psoriasis pathogenesis via the direct regulation of dermal IL-17-producing cells and stimulation of keratinocytes for amplifying inflammatory cascade.
- Local production of prolactin in lesions may play a pathogenic role in psoriatic patients and imiquimod-induced psoriasis-like mouse model. [Journal Article]
- EDExp Dermatol 2018 Aug 18
- Human prolactin (PRL) is a well-known hormone for pituitary of lactation and reproduction, but it also has immunostimulatory effect in some inflammatory or autoimmune diseases including psoriasis, wh...
Human prolactin (PRL) is a well-known hormone for pituitary of lactation and reproduction, but it also has immunostimulatory effect in some inflammatory or autoimmune diseases including psoriasis, which has not been well elucidated. This study aimed to determine the relationship between PRL and psoriasis through clinical case-control studies, and explore the function of PRL in the pathogenesis of imiquimod (IMQ)-induced psoriasis-like mouse model. Serum from patients with psoriasis vulgaris (PsV), patients with erythrodermic psoriasis, and healthy controls (HCs) were collected for PRL test. Skin biopsies were collected for PRL, PRL receptors (PRLRs), cytokines mRNA level determination, PRL immunohistochemistry and PRL western blotting. Mice were divided into 4 groups (each n=6): control group (CON), IMQ group, anti-PRL group and solvent group. Anti-PRL group and solvent group mice were treated with PRL antagonist (cabergoline) and the solvent (0.25% methylcellulose) separately. The serum PRL level of PsV patients was significantly higher than that of HCs (P<0.001). Compared with HCs, the mRNA levels of PRL and Th1/Th17 cytokines in skin lesions increased significantly (P<0.05), and the PRL protein level was also significantly elevated in the epidermis and dermis of PsV patients. In IMQ-induced psoriasis-like mouse model, the mRNA and protein levels of PRL in skin lesions were significantly higher than CON group (P<0.01). Comparing to solvent group, serum PRL level and PRL, cytokines mRNA levels in skin lesions all decreased significantly and the skin inflammatory condition was also alleviated obviously in anti-PRL group. This study suggests that local production of PRL is the main resource of PRL in skin lesions and may play an important role in skin inflammatory of psoriasis. This article is protected by copyright. All rights reserved.
- Experience with Treating Lentigo Maligna with Definitive Radiotherapy. [Review]
- DRDermatol Res Pract 2018; 2018:7439807
- Lentigo maligna (LM) is a form of melanoma in situ that occurs on exposed, sun-damaged skin; LM can progress to invasive melanoma. Conventional surgical treatment is the preferred management option a...
Lentigo maligna (LM) is a form of melanoma in situ that occurs on exposed, sun-damaged skin; LM can progress to invasive melanoma. Conventional surgical treatment is the preferred management option as it is usually a one-treatment episode and generates a histopathology report that records completion of excision. Some patients may not be surgical candidates due to comorbidities, patient preference, impact on function, and cosmesis or they have failed surgery with a positive margin. Other therapies, including radiotherapy (RT) and topical medicines, may then become appropriate. There is a currently accruing multi-institutional randomized trial of imiquimod versus definitive RT for this population (NCT02394132). This review is about the experience from the centre that has generated the trial and enrolled the most patients to date. The purpose of the review is to pass on experience to other centers who may want to join the trial, especially to supplement the experience of local radiation oncologists. The review covers decisions that need to be made in RT planning and treatment and how to manage side effects and other common scenarios including LM in immunosuppressed patients and in poorly vascularised tissue, after surgery, of the eyelid and of mucous membrane (mouth and nose) that are in the radiation field.
- TLR7-let7 signaling contributes to ethanol-induced hepatic inflammatory response in mice and in alcoholic hepatitis. [Journal Article]
- ACAlcohol Clin Exp Res 2018 Aug 13
- Toll like receptor 7 (TLR7) is an endosomal TLR that is activated by ssRNA, including endogenous microRNAs (e.g. let-7b). Increased hepatic expression of TLRs, microRNAs, and inflammatory mediators a...
Toll like receptor 7 (TLR7) is an endosomal TLR that is activated by ssRNA, including endogenous microRNAs (e.g. let-7b). Increased hepatic expression of TLRs, microRNAs, and inflammatory mediators are linked to ethanol exposure and to alcoholic liver disease (ALD). ALD invovles chronic hepatic inflammation that can progress to alcoholic hepatitis (AH), a particularly severe form of ALD. This study aimed to investigate TLR7 expression in patients with different liver disease phenotypes and in mouse liver following alcohol exposure.
- Resolvin E1 attenuates murine psoriatic dermatitis. [Journal Article]
- SRSci Rep 2018 Aug 08; 8(1):11873
- The potential of omega-3 poly-unsaturated fatty acids (PUFAs) as a therapeutic target for psoriasis, a chronic inflammatory skin disease of IL-23/IL-17 axis, is a long-disputed question, since variou...
The potential of omega-3 poly-unsaturated fatty acids (PUFAs) as a therapeutic target for psoriasis, a chronic inflammatory skin disease of IL-23/IL-17 axis, is a long-disputed question, since various epidemiological studies have suggested the association between high-intake of omega-3 PUFAs and the reduced frequency and severity of psoriasis. However, their actual significance and the molecular mechanisms remain largely unknown. To address these issues, we focused on resolvin E1 (RvE1), an omega-3 PUFAs-derived metabolite, and examined its effects on psoriatic dermatitis, using an imiquimod-induced mouse psoriasis model. RvE1 potently suppressed the inflammatory cell infiltration and epidermal hyperplasia in the psoriatic skin. RvE1 decreased the mRNA expression of IL-23 in the skin. Consistently, RvE1 inhibited IL-23 production by dendritic cells (DCs) in vitro. Furthermore, RvE1 exerted inhibitory effects on migration of cutaneous DCs and γδ T cells, a major IL-17-producing cell population in mouse, both in vivo and in vitro. These suppressive effects of RvE1 were mediated by its antagonistic function on BLT1, a receptor of leukotriene B4, and were also observed in human DCs, Th17 and Tc17 cells. Our results indicate a novel mechanism of omega-3 PUFA-mediated amelioration of psoriasis, and suggest a potential of RvE1 as a therapeutic target for psoriasis.
- Epithelial TRAF6 drives IL-17-mediated psoriatic inflammation. [Journal Article]
- JIJCI Insight 2018 Aug 09; 3(15)
- Epithelial cells are the first line of defense against external dangers, and contribute to induction of adaptive immunity including Th17 responses. However, it is unclear whether specific epithelial ...
Epithelial cells are the first line of defense against external dangers, and contribute to induction of adaptive immunity including Th17 responses. However, it is unclear whether specific epithelial signaling pathways are essential for the development of robust IL-17-mediated immune responses. In mice, the development of psoriatic inflammation induced by imiquimod required keratinocyte TRAF6. Conditional deletion of TRAF6 in keratinocytes abrogated dendritic cell activation, IL-23 production, and IL-17 production by γδ T cells at the imiquimod-treated sites. In contrast, hapten-induced contact hypersensitivity and papain-induced IgE production were not affected by loss of TRAF6. Loss of psoriatic inflammation was not solely due to defective imiquimod sensing, as subcutaneous administration of IL-23 restored IL-17 production but did not reconstitute psoriatic pathology in the mutant animals. Thus, TRAF6 was required for the full development of IL-17-mediated inflammation. Therefore, epithelial TRAF6 signaling plays an essential role in both triggering and propagating IL-17-mediated psoriatic inflammation.
- Pagetoid Dyskeratosis of the Male Genitalia: Case Report and Review. [Journal Article]
- CCureus 2018 Jun 01; 10(6):e2727
- Pagetoid dyskeratosis is a benign incidental pathologic finding that has been reported in many distinct skin lesions on various locations of the body. A man who had pagetoid dyskeratosis within lesio...
Pagetoid dyskeratosis is a benign incidental pathologic finding that has been reported in many distinct skin lesions on various locations of the body. A man who had pagetoid dyskeratosis within lesions of the penile shaft is described and similar cases of pagetoid dyskeratosis in lesions of the male genitalia are reviewed. The patient was a 26-year-old healthy man who developed several asymptomatic penile papules that were refractory to topical imiquimod 5% cream and cryotherapy. Snip biopsies were performed and microscopic examination revealed pagetoid dyskeratosis. PubMed was searched for the following terms: cell, clear, dyskeratosis, genitalia, pagetoid, penile, penis, prepuce, scrotum, and shaft. The papers containing these terms and their references were reviewed. Pagetoid dyskeratosis has been observed in lesions on the prepuce and scrotum; this case report now expands the distribution of this finding to the penile shaft. Clinicians and pathologists should be aware of this intriguing potential incidental finding within skin lesions of the male genitalia.
- Actinic keratosis - review for clinical practice. [Review]
- IJInt J Dermatol 2018 Aug 02
- Actinic keratosis (AK) is a lesion that arises as a result of excessive exposure to solar radiation and appearing predominantly on Fitzpatrick phototype I and II skin. Given that some AKs evolve into...
Actinic keratosis (AK) is a lesion that arises as a result of excessive exposure to solar radiation and appearing predominantly on Fitzpatrick phototype I and II skin. Given that some AKs evolve into squamous cell carcinoma, these lesions are considered premalignant in nature, occurring mostly in elderly men and immunosuppressed individuals chronically exposed to ultraviolet (UV) radiation. There are several mechanisms for the formation of AKs; among them are oxidative stress, immunosuppression, inflammation, altered proliferation and dysregulation of cell growth, impaired apoptosis, mutagenesis, and human papillomavirus (HPV). Through the understanding of these mechanisms, several treatments have emerged. Among the options for AK treatment, the most commonly used include 5-fluorouracil (5-FU), cryotherapy, diclofenac, photodynamic therapy (PDT), imiquimod (IQ), retinoids, and ingenol mebutate (IM). There have been recent advances in the treatment options that have seen the emergent use of newer agents such as resiquimod, betulinic acid, piroxicam, and dobesilate. The combination between therapies has presented relevant results with intention to reduce duration of therapy and side effects. All AK cases must be treated because of their propensity to transform into malignancy and further complicate treatment. In addition to medical or surgical care, education about sun exposure prevention remains the best and most cost-effective method for AK prevention. The objective of this article is to conduct a literature review of the clinical presentation of AK including advances in treatment options available.
- Effectiveness of physically ablative and pharmacological treatments for anal condyloma in HIV-infected men. [Journal Article]
- PlosPLoS One 2018; 13(8):e0199033
- CONCLUSIONS: Recurrence of anal condyloma after any treatment was common. Abnormal anal cytology and high-risk HPV-infection were highly prevalent in this population, therefore at high-risk of anal cancer, and warrants careful follow-up.
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- Daylight photodynamic therapy for the treatment of actinic cheilitis. [Journal Article]
- PPPhotodermatol Photoimmunol Photomed 2018 Jul 31
- CONCLUSIONS: Daylight PDT is a promising modality for the treatment of AC, with impressive cosmetic results and few side effects.