Protective effect of Yangxue Jiedu Soup against psoriasis-like lesions by regulating TLR4/NF-κB signaling pathway mediated by secretion of exosome HSP70.

Psoriasis is a common chronic inflammatory hypertrophic skin disease characterized by abnormal proliferation and differentiation of keratinocyte and immune T cell. The pathogenesis of psoriasis has not been fully elucidated and there is no effective therapy in clinic. As a traditional Chinese medicine formula, Yangxue Jiedu Soup (YJS) has been used to treat inflammatory diseases caused by Yin Deficiency and Blood Dryness. The purpose of present study was to investigate the therapeutic effect and molecular mechanism of YJS on psoriasis model mice. Results showed that YJS effectively inhibited the hypertrophy, erythema and scales of psoriasis-like lesions to alleviate the pathological changes of skin lesions, and further decreased the production of TNF-α, IL-6, IL-1ß, IFN-γ, IL-17 and IL-23. Meanwhile, YJS also significantly reduced keratinocyte proliferation and maintained immune system balance by inhibiting the expression of PCNA, Ki-67, CD4 + and CD8 + in psoriasis mice. Moreover, the results further indicated that YJS could inhibit TLR4 activation and NF-κB p65 nuclear transfer by suppressing HSP70 secretion to attenuate the inflammatory response in IMQ-induced mice, which provided a theoretical basis for the clinical use of YJS in the treatment of psoriasis.

Randialic acid B and tomentosolic acid block formyl peptide receptor 1 in human neutrophils and attenuate psoriasis-like inflammation in vivo.

Psoriasis is a long-lasting inflammatory skin disease lacking proper cure. Dysregulated activation of neutrophils is a major pathogenic factor in psoriasis. Formyl peptide receptor 1 (FPR1) triggers neutrophil activation in response to bacteria- or mitochondria-derived N-formyl peptides, but its significance in neutrophilic psoriasis remains unknown. In this study, we discovered two derivatives of ursolic acid, 3ß-hydroxyurs-12,18-dien-28-oic acid (randialic acid B, RAB) and 3ß-hydroxyurs-12,19-dien-28-oic acid (tomentosolic acid, TA), as FPR1 inhibitors in human neutrophils with ability to suppress psoriatic symptoms in mice. Both RAB and TA, triterpenoids of traditional medicinal plant Ilex kaushue, selectively inhibited reactive oxygen species production, elastase release, and CD11b expression in human neutrophils activated by FPR1, but not non-FPR1 agonists. Importantly, RAB and TA inhibited the binding of N-formyl peptide to FPR1 in human neutrophils, neutrophil-like THP-1 cells, and hFPR1-transfected HEK293 cells, indicating FPR1 antagonism. Moreover, in assays induced by various concentrations of FPR1 agonist, both RAB and TA acted competitively for its binding to the FPR1 receptor. The FPR1-downstream signaling such as Ca2+ mobilisation and activation of Akt and MAPKs was also competitively inhibited. In addition, imiquimod-induced psoriasis-like symptoms, including epidermal hyperplasia, desquamation with scaling, neutrophil skin infiltration, and transepidermal water loss were significantly reduced by both RAB and TA. The results illustrate a possible role of human neutrophils FPR1 receptor in psoriasis-like inflammation. Accordingly, triterpenoids RAB and TA represent novel FPR1 antagonists and exhibit therapeutic potential for treating neutrophilic inflammatory skin diseases.

Curcuma's extraction attenuates propranolol-induced psoriasis like in mice by inhibition of keratin, proliferating cell nuclear antigen and toll-like receptor expression.

Curcuma was the dried rhizomes of Curcuma kwangsiensis S.G. Lee et C.F. Liang (Chinese name: e zhu), have been used in China for thousands of years. There are some reports have shown that curcumin, the major component of curcuma, has a good curative effect on psoriasis, but the mechanism is still unknown, so the present study was designed to investigate the effect of curcuma's extraction on psoriasis-like mouse, and to explore the mechanisms of therapy. First, we observed that curcuma's extractions effect on mitosis of mouse vaginal epithelial cells; then making psoriasis like model and measuring the score of skin damage on days 7 and 14; finally, we observed the expression of immune factors (CK14, CK16, CK17, PCNA, TLR-2, TLR-4, TLR-9) in propranolol induced psoriasis like rats. Curcuma's extraction prohibited the mitosis of mouse vaginal epithelial cells; curcuma's extractions have a significantly efficacy and dose dependent inhibition on imiquimod induced psoriasis like rats; and the expression of immune factors (CK14, CK16, CK17, PCNA, TLR-2, TLR-4, TLR-9) was decreasing in the curcuma's extraction treated groups compared with normal groups. Our research proved that curcuma's extractions have a significantly efficacy on psoriasis like rats, thus, curcuma's extractions can be a potential novel treatment for psoriasis. Furthermore, the expression of immune factors was decreasing after treatment with curcuma's extraction suggest us cytokines has strong relation with the mechanism of therapy for psoriasis. Our results contribute towards validation of curcuma in the treatment of psoriasis and other joint disorders.

Anti-psoriatic effect of Lavandula angustifolia essential oil and its major components linalool and linalyl acetate.

ETHNO-PHARMACOLOGICAL RELEVANCE: Lavender oil (LO) is an aromatic/essential oil extracted from Lavandula angustifolia and traditionally used as an aromatherapy massage oil due to its anti-inflammatory and wound healing property and also for providing the relief in other skin conditions such as psoriasis, dermatitis and eczema. However, LO has not been evaluated scientifically for psoriasis like skin inflammation. AIM OF THE STUDY: This study was aimed to investigate the LO and its major components linalool (L) and linalyl acetate (LA) against psoriasis like skin inflammation. MATERIALS AND METHODS: Anti-psoriatic activity was done using Imiquimod (IMQ) induced psoriasis like skin inflammation in BALB/c mice. Assessment of anti-psoriatic effect of LO, L and LA was done on the basis of change in ear thickness, psoriasis area severity index (PASI) scoring at alternative day, CosCam scoring using skin analyzer equipped with SkinSys software, biochemical, immunohistochemical and histological investigations. Level of effectiveness against psoriasis was investigated by percent reduction in PASI scores, CosCam scores and level of Th-1 and Th-17 cell expressing cytokines, as compared to the diseased mice. RESULTS: Topical application of LO 10% showed 73.67% recovery in PASI and 87% in Th-17 cell-specific cytokines towards normal as compared to disease group. L and LA were identified as the major components of LO and favoured ligands for selected psoriasis targets. At 2% topical dose, L and LA showed 64% and 47.61% recovery in PASI scores, respectively. Both, L and LA showed significant recovery in Th-1 specific TNF-α and IL-1ß however, only L showed significant recovery of Th-17 cytokines (IL-17 and IL-22). In contrast to LA (which restored granulosis), L restored epidermal hyperplasia and parakeratosis toward the normal condition. On the other hand, L also reduced the expression of NF-κß, ccr6 and IL-17, while LA reduced the expression of NF-κß only. At 10% topical dose, LO was observed to be slight irritant while at 2% topical dose, L and LA were found non-irritant to the skin. CONCLUSION: This study proves the effectiveness of LO and its major phytoconstituents linalool and linalyl acetate against IMQ induced psoriasis like skin inflammation and provides the scientific evidence for topical use of lavender oil.

The anti-TH17 polarization effect of Indigo naturalis and tryptanthrin by differentially inhibiting cytokine expression.

ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese herbal medicine Qing-Dai (also known as Indigo naturalis) extracted from indigo-bearing plants including Baphicacanthus cusia (Ness) Bremek was previously reported to exhibit anti-psoriatic effects in topical treatment. TH17 was later established as a key player in the pathogenesis of psoriasis. We investigated the anti-TH17 effect of Indigo naturalis and its active compounds. The aim of this study is to evaluate the toxicity of Indigo naturalis (IN) and its derivatives on five cell types involved in psoriasis, and to study the anti-inflammatory mechanism for the toxicity. MATERIALS AND METHODS: Following the fingerprint and quantity analysis of indirubin, indigo, and tryptanthrin in IN extract, we used MTS kits to measure the anti-proliferative effect of IN and three active compounds on five different cell types identified in psoriatic lesions. Quantitative RT-PCR analysis was used to measure the expression of various genes identified in the activated keratinocytes and TH17 polarized gene expression in RORγt-expressing T cells. RESULTS: We showed that IN differentially inhibited the proliferation of keratinocytes and endothelial cells but not monocytes, fibroblasts nor Jurkat T cells. Among three active compounds identified in IN, tryptanthrin was the most potent compound to reduce their proliferation. In addition to differentially reducing IL6 and IL8 expression, both IN and tryptanthrin also potently decreased the expression of anti-microbial S100A9 peptide, CCL20 chemokine, IL1B and TNFA cytokines, independent of NF-κB-p65-activation. Their attenuating effect was also detected on the expression of signature cytokines or chemokines induced during RORγT-induced TH17 polarization. CONCLUSIONS: We were the first to confirm a direct anti-TH17 effect of both IN herbal extract and tryptanthrin.

Omega-3 Versus Omega-6 Polyunsaturated Fatty Acids in the Prevention and Treatment of Inflammatory Skin Diseases.

Omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) are nowadays desirable components of oils with special dietary and functional properties. Their therapeutic and health-promoting effects have already been established in various chronic inflammatory and autoimmune diseases through various mechanisms, including modifications in cell membrane lipid composition, gene expression, cellular metabolism, and signal transduction. The application of ω-3 and ω-6 PUFAs in most common skin diseases has been examined in numerous studies, but their results and conclusions were mostly opposing and inconclusive. It seems that combined ω-6, gamma-linolenic acid (GLA), and ω-3 long-chain PUFAs supplementation exhibits the highest potential in diminishing inflammatory processes, which could be beneficial for the management of inflammatory skin diseases, such as atopic dermatitis, psoriasis, and acne. Due to significant population and individually-based genetic variations that impact PUFAs metabolism and associated metabolites, gene expression, and subsequent inflammatory responses, at this point, we could not recommend strict dietary and supplementation strategies for disease prevention and treatment that will be appropriate for all. Well-balanced nutrition and additional anti-inflammatory PUFA-based supplementation should be encouraged in a targeted manner for individuals in need to provide better management of skin diseases but, most importantly, to maintain and improve overall skin health.

PSORI-CM02 formula alleviates imiquimod-induced psoriasis via affecting macrophage infiltration and polarization.

AIMS: Psoriasis is a refractory skin disease characterized by macrophage cell infiltrated in the dermal layer. Macrophages can simultaneously polarize into two distinct functional subtypes, M1 and M2, and this process is affected by the microenvironment, cytokines and JAK/STAT pathways. Formula PSORI-CM02 is a novel Chinese medicine used to alleviate psoriasis symptoms and regulate T cell differentiation and epithelial cell proliferation. However, the effects of PSORI-CM02 in imiquimod (IMQ)-induced psoriasis and macrophage infiltration and polarization in the dermis remain unknown. MAIN METHODS: Imiquimod induced psoriasis mice model and M1/M2 polarization model on mice peritoneal macrophages cell line RAW264.7 in vitro were used to observe the therapeutic effect of PSORI-CM02 on skin and its molecular mechanisms. KEY FINDINGS: PSORI-CM02 can significantly improve skin lesions and reduce macrophage infiltration in mice induced by imiquimod. After treatment with PSORI-CM02 formula, M1 macrophage mediators were significantly reduced, while M2 mediators were significantly increased in mice. Similarly in vitro, M1 macrophage proliferation was suppressed and M2 macrophage proliferation was elevated by PSORI-CM02 in the presence of LPS and IL-4, respectively. The elevated expression of TNF-α, iNOS, and IL-1ß induced by LPS was reduced, while the expression of Arg-1, Fizz-1, Ym-1, and IL-10 induced by IL-4 was elevated in PSORI-CM02-treated cells. Finally, we found that the effects of PSORI-CM02 in macrophage polarization were associated with regulation of STAT1 and STAT6 expression, which were activated by LPS and IL-4, respectively. SIGNIFICANCE: Our novel findings reveal that PSORI-CM02 may possess therapeutic action in psoriasis treatment by regulating the infiltration and polarization of macrophages in the dermal layer.

The impact of diet on psoriasis.

Because psoriasis is a chronic and inflammatory disease, many patients seek alternative therapies and lifestyle modifications to supplement their treatments and help relieve symptoms. Both the disease and the modifications are multifactorial, making it difficult to quantify the effectiveness of a single change. A review of the available literature reveals that most diets have mixed impacts on psoriasis, though some individual foods have seen more prominence in studies. Foods and supplements with systemic anti-inflammatory effects seem to have a higher chance of improving psoriasis symptoms. Overall, additional large-population studies with a higher statistical power are needed to review these studies. We suggest web-based national cohort surveys as a possible method to quickly gather a large amount of data for future studies.

Chitosan-based nanoformulated (-)-epigallocatechin-3-gallate (EGCG) modulates human keratinocyte-induced responses and alleviates imiquimod-induced murine psoriasiform dermatitis.

BACKGROUND: Psoriasis is a chronic and currently incurable inflammatory skin disease characterized by hyperproliferation, aberrant differentiation, and inflammation, leading to disrupted skin barrier function. The use of natural agents that can abrogate these effects could be useful for the treatment of psoriasis. Earlier studies have shown that treatment of keratinocytes and mouse skin with the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) mitigated inflammation and increased the expression of caspase-14 while promoting epidermal differentiation and cornification. However, bioavailability issues have restricted the development of EGCG for the treatment of psoriasis. MATERIALS AND METHODS: To overcome these limitations, we employed a chitosan-based polymeric nanoparticle formulation of EGCG (CHI-EGCG-NPs, hereafter termed nanoEGCG) suitable for topical delivery for treating psoriasis. We investigated and compared the efficacy of nanoEGCG versus native or free EGCG in vitro and in an in vivo imiquimod (IMQ)-induced murine psoriasis-like dermatitis model. The in vivo relevance and efficacy of nanoEGCG formulation (48 µg/mouse) were assessed in an IMQ-induced mouse psoriasis-like skin lesion model compared to free EGCG (1 mg/mouse). RESULTS: Like free EGCG, nanoEGCG treatment induced differentiation, and decreased proliferation and inflammatory responses in cultured keratinocytes, but with a 4-fold dose advantage. Topically applied nanoEGCG elicited a significant (p<0.01) amelioration of psoriasiform pathological markers in IMQ-induced mouse skin lesions, including reductions in ear and skin thickness, erythema and scales, proliferation (Ki-67), infiltratory immune cells (mast cells, neutrophils, macrophages, and CD4+ T cells), and angiogenesis (CD31). We also observed increases in the protein expression of caspase-14, early (keratin-10) and late (filaggrin and loricrin) markers of differentiation, and the activator protein-1 factor (JunB). Importantly, a significant modulation of several psoriasis-related inflammatory cytokines and chemokines was observed compared to the high dose of free EGCG (p<0.05). Taken together, topically applied nanoEGCG displayed a >20-fold dose advantage over free EGCG. CONCLUSION: Based on these observations, our nanoEGCG formulation represents a promising drug-delivery strategy for treating psoriasis and possibly other inflammatory skin diseases.

8-Methoxypsoralen Plus Ultraviolet A Reduces the Psoriatic Response to Imiquimod in a Murine Model.

The effects of 8-Methoxypsoralen plus ultraviolet A (PUVA) or ultraviolet B (UVB) alone on imiquimod-induced psoriasis were examined in a mouse model. Mouse skin was treated with repetitive sub-phototoxic doses of PUVA or UVB before or during the induction of toll-like receptor 7/8 activation and psoriasis through the application of imiquimod. PUVA, to a greater degree than UVB, suppressed the established imiquimod-induced psoriatic phenotype, but pretreatment with PUVA prior to administration of imiquimod also reduced the susceptibility of murine skin to respond to imiquimod to a greater degree than did pretreatment with UVB. PUVA downregulated baseline levels of miRNA27a and 29a, as well as interferon-γ, interleukin-17 and -9, cytokines, which drive psoriatic inflammation. Microarray analysis showed enrichment of senescence pathway genes linked to upregulation of p16/p21 proteins after PUVA pretreatment. However, the anti-psoriatic effect of PUVA was lost when there was an interval of 7 days between final exposure to PUVA and the start of administration of imiquimod. This indicated that (UVB and) PUVA diminished imiquimod-induced established psoriatic inflammation, but also primed the skin in favour of a reduced responsiveness to toll-like receptor activation.

Therapeutic Effects of Methanol Extract from Euphorbia kansui Radix on Imiquimod-Induced Psoriasis.

The roots of Euphorbia kansui, which belong to the family Euphorbiaceae, have been used as a traditional medicine for the treatment of various diseases such as diabetes, ascites, and leukemia. Recently, it was reported that the methylene chloride fraction of E. kansui radix (EKC) regulated the differentiation of Th17 cells and alleviated the symptoms of Th17-related inflammatory bowel disease. Imiquimod (IMQ), a TLR7/8 agonist, has been used to induce psoriasis in a mouse model. In this study, we evaluated the effect of EKC in an IMQ-induced psoriasis model. EKC effectively inhibited the production of interleukin-17A and interferon-γ in vitro. On this basis, EKC was administered to an animal model of psoriasis. Acanthosis and the infiltration of inflammatory cells into the dermis were significantly reduced by EKC. EKC also inhibited the expression of IL-17A, IL-22, IL-23, IL-12, and RAR-related orphan receptor gamma t (RORγt) in the spleen, skin-draining lymph nodes, and the skin. Additionally, EKC inhibited the activity of dendritic cells but not that of keratinocytes. In conclusion, EKC ameliorated the symptoms of psoriasis through inhibition of Th17 differentiation and activation of dendritic cells. These effects are expected to be beneficial in the treatment and prevention of psoriasis.

Treatment preferences for biologicals in psoriasis: experienced patients appreciate sustainability.

BACKGROUND AND OBJECTIVES: Treatment satisfaction can be improved by integrating patients' preferences into shared decision-making. We recently investigated patients' preferences for attributes of biologicals, and showed high preferences for safety and efficacy. The objective of the present study was to assess the impact of treatment experience on these preferences. PATIENTS AND METHODS: Preferences for outcome (probability of 50 % and 90 % improvement, time until response, sustainability of success, probability of mild and severe adverse events, probability of ACR 20 response) and process attributes (treatment location, frequency, duration, and delivery method) were analyzed in 200 participants with moderate-to-severe psoriasis using conjoint analysis. The impact of current and previous therapies, disease duration, and treatment satisfaction on 'Relative Importance Scores' was determined by analysis of variance, post hoc tests, and multivariate regression. RESULTS: Participants presently on topical therapy (p = 0.02) or phototherapy (p = 0.032) placed more importance on treatment duration than others. Individuals who had previously been given traditional systemic agents (p = 0.028) or biologicals (p = 0.044) favored sustainability more than others. With an increasing number of systemic agents ever received (p = 0.045) and longer disease duration (p = 0.018), the latter attribute became increasingly important. CONCLUSIONS: Patients' preferences for biologicals vary in correlation with treatment experience and disease duration, aspects to be addressed in the context of shared decision-making.

BAY 11-7082 inhibits the NF-κB and NLRP3 inflammasome pathways and protects against IMQ-induced psoriasis.

BAY 11-7082 antagonizes I-κB kinase-ß preventing nuclear translocation of nuclear factor-κB (NF-κB); it also inhibits NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation. NF-κB is involved in psoriasis, whereas the role of NLRP3 is controversial. We investigated BAY 11-7082 effects in an experimental model of psoriasis-like dermatitis. Psoriasis-like lesions were induced by a topical application of imiquimod (IMQ) cream (62.5 mg/day) on the shaved back skin of C57BL/6 and NLRP3 knockout (KO) mice for 7 consecutive days. Sham psoriasis animals were challenged with Vaseline cream. Sham and IMQ animals were randomized to receive BAY 11-7082 (20 mg/kg/i.p.) or its vehicle (100 µl/i.p of 0.9% NaCl). Skin of IMQ animals developed erythema, scales, thickening and epidermal acanthosis. IMQ skin samples showed increased expression of pNF-κB and NLRP3 activation. BAY 11-7082 blunted epidermal thickness, acanthosis and inflammatory infiltrate. BAY 11-7082 reduced pNF-κB, NLRP3, tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß expression, blunted the phosphorylation of signal transducer and activators of transcription 3 (STAT3) and decreased IL-23 levels. In addition, BAY 11-7082 reawakened the apoptotic machinery. NLRP3 KO animals showed a reduced total histological score but persistent mild acanthosis, dermal thickness and expression of pNF-κB and pSTAT3, following IMQ application. Our data suggest that BAY 11-7082 might represent an interesting approach for the management of psoriasis-like dermatitis depending on the dual inhibition of NF-κB and NLRP3.

Anti-proliferative and anti-inflammatory effects of 3ß,6ß,16ß-Trihydroxylup-20(29)-ene on cutaneous inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: 3ß,6ß,16ß-Trihydroxylup-20(29)-ene (TTHL) is a triterpene isolated from the flowers of Combretum leprosum, a plant used in folk medicine in the north of Brazil for the treatment of skin disorders. AIM OF THE STUDY: In the present study, TTHL was evaluated as a potential topical anti-inflammatory and anti-proliferative agent through in vivo and in vitro models. MATERIAL AND METHODS: Anti-inflammmatory and anti-proliferative effects of TTHL were assessed using Swiss mice in acute and chronic models of skin inflammation induced by 12-O-tetradecanoylphorbol-acetate (TPA) application. Anti-proliferative activity was proved through in vitro experiments with the HaCaT human keratinocyte cell line. RESULTS: Treatment with TTHL inhibited inflammatory parameters such as oedema formation and cellular infiltration in acute and chronic models. In the chronic model, TTHL also inhibited epidermal hyperproliferation, as evidenced by reduction of epidermis thickness and proliferating cell nuclear antigen expression. The anti-proliferative effect was confirmed by the capability of TTHL in reducing the proliferation and inducing cell apoptosis of HaCaT cells. Suggesting a mechanism of action, TTHL showed activation of corticosteroid receptors, but without the induction of corticosteroid-related cutaneous side effects. CONCLUSION: Our results demonstrate consistent anti-inflammatory and anti-proliferative activity and assign TTHL as a valuable tool in the development of a new treatment for skin inflammatory and proliferative diseases, such as psoriasis.

Evaluation of potent phytomedicine for treatment of psoriasis using UV radiation induced psoriasis in rats.

The aim of present study was to determine the effect of newly formulated gels and suspensions of extractive Phytoconstituents of Woodfordia fructicosa flowers and Gardenia gummifera leaves by using UV Radiation induced psoriasis in rats. Both plants are traditionally claimed to be useful in treatment of number of skin diseases. However, there are no established scientific reports for their potential in psoriasis. Formulated Gels and Suspensions of ethanolic extract of both plants were tested for acute dermal and oral toxicity study respectively. The results of acute dermal toxicity at concentration 1% w/w and oral toxicity at dose 1000mg/kg showed that the gels and suspensions were safe. Psoriasis was induced in Wistar rats by espousing 10% area of total body by UV radiations. Anti-psoriatic activity was performed by applying 0.1% gel and orally at a dose 100mg/kg body weight in rats. Severity Index, histological study and biochemical estimation were analyzed. The results of our studies showed that the test formulations (Gels and Suspensions) of both plant extracts exhibited potential effect in anti-psoriatic activity.

Terminalia Chebulanin Attenuates Psoriatic Skin Lesion via Regulation of Heme Oxygenase-1.

BACKGROUND/AIMS: Psoriasis is one of the most common inflammatory skin disorders, affecting 3% of the general population. Terminalia chebulanin (TC) is a polyphenolic compound that possesses antioxidant and anti-inflammatory activities. The current study was designed to investigate the effect of TC on psoriatic lesions. METHODS: We examined the protective effect of TC against psoriatic lesions in mice and keratinocyte proliferation in HaCaT cells. RESULTS: We found that TC exhibited potent anti-psoriatic activities, as evidenced by improvement of erythema and scaling scores, decrease of epidermal, ear and skinfold thickening, decrease of tumor necrosis factor α (TNFα), interleukin (IL)-17A, IL-23 and matrix metalloproteinase (MMP)-9 expression, and decrease of TBARS content and increase of GSH content in IMQ-treated mice, and decrease of keratinocyte proliferation, TNFα, IL-17A and IL-23 expression, and ROS level in M5-treated cells. All those effects induced by TC were inhibited by zinc protoporphyrin IX (ZnPP), an inhibitor of heme oxygenase (HO)-1, indicating that HO-1 was responsible the anti-psoriatic effect of TC. Moreover, TC inhibited the upregulation of p65 NF-x03BA;B under in vitro psoriatic condition. ZnPP suppressed TC-induced inhibition of p65 NF-x03BA;B expression. Overexpression of p65 NF-x03BA;B significantly suppressed TC-induced decrease of TNFα, IL-17A and IL-23 expression and keratinocyte proliferation, indicating that HO-1-mediated downregulation of NF-x03BA;B was involved in the anti-psoriatic effect of TC. CONCLUSIONS: The data demonstrate that TC may serve as a potential therapeutic option for psoriatic patients.

Multi-glycoside of Tripterygium wilfordii Hook. f. ameliorates imiquimod-induced skin lesions through a STAT3-dependent mechanism involving the inhibition of Th17-mediated inflammatory responses.

Multi-glycoside of Tripterygium wilfordii Hook. f.(GTW) possesses anti-inflammatory and immunosuppressive properties, and has been used as a traditional treatment for psoriasis for many years, although the underlying immunological mechanisms remain poorly understood. The T helper (Th)17 cell response is considered to play a major role in the pathogenesis of psoriasis. Th17 cells are implicated in the mechanism of pathogenesis of imiquimod (IMQ)­induced skin inflammation. Using a mouse model, we demonstrated that GTW protected mice from developing psoriasis-like lesions induced by topical IMQ administration. This protection was associated with significantly decreased mRNA levels of Th17 cytokines such as interleukin (IL)-17A, IL-17F and IL-22 in mouse skin samples as well as fewer IL-17-secreting splenic CD4+ lymphocytes in IMQ-exposed mice. There were no significant effects on the proportion of CD4+ interferon (IFN)-γ+ T cells, CD4+IL-4+ T cells and CD4+CD25+Foxp3+ Treg cells in the spleen cells. Taken together with the unchanged mRNA levels of Th1 cytokine IFN-γ, Th2 cytokine IL-4 and Treg cytokine IL-10 in IMQ-exposed mouse skin following GTW administration, our findings suggest that the immunosuppressive effect of GTW in psoriasis is exerted mainly on Th17 cells, rather than on Th1, Th2 or Treg cells. Furthermore, we showed that GTW suppressed Th17 function through the inhibition of STAT3 phosphorylation. These results have the potential to pave the way for the use of GTW as an agent for the treatment of psoriasis.

Severe Psoriasis Flare After Anti-Programmed Death Ligand 1 (PD-L1) Therapy for Metastatic Non-Small Cell Lung Cancer (NSCLC).

Immunomodulatory agents that target PD-1 and its ligand (PD-L1) are being increasingly used in the management of lung cancer. Potential immune-related adverse events include dermatological complications which mostly are of low grade severity. The use of immune checkpoint inhibitors may lead to the exacerbation of autoimmune conditions. We report a case of a documented psoriasis flare with anti-PD-1 treatment for lung cancer.

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