scholarly journals IL-36γ promotes psoriasis-like features in keratinocytes in an imiquimod-induced murine model of psoriasis

2022 ◽  
Author(s):  
Wen-Ming Wang ◽  
Chao Wu ◽  
Yi-Meng Gao ◽  
Hong-Zhong Jin
Keyword(s):  
Severity Index ◽  
Skin Lesions ◽  
Interferon Γ ◽  
Inflammatory Skin Disease ◽  
Epidermal Thickness ◽  
Differentiation Markers ◽  
Keratin 5 ◽  
Inflammatory Phenotype ◽  
Heavy Burden ◽  
Deficient Mice

IntroductionPsoriasis is a recurrent, chronic inflammatory skin disease with complex pathogenesis. The disease imposes a heavy burden on patients. Interleukin (IL)-36γ belongs to the IL-36 family and is predominantly expressed by epithelial cells. IL-36γ is upregulated in psoriasis lesions. However, the effects of IL-36γ in keratinocytes remain unclear.Material and methodsEighteen IL-36γ-deficient mice were divided into three groups: the vaseline group, the imiquimod (IMQ) group, and the IMQ/IL-36γ group. Vaseline or IMQ was administered for 6 consecutive days. The severity of psoriasis-like lesions was evaluated using a modified Psoriasis Area and Severity Index (PASI) scoring system. Production of cytokines and expression of differentiation markers were assessed by immunohistochemistry.ResultsIMQ-induced psoriasis lesions were significantly more severe in IMQ/IL-36γ-treated mice compared with vaseline-treated and IMQ-treated mice, as shown by an exacerbated inflammatory phenotype, increased numbers of blood vessels, increased infiltration of cells, and increased epidermal thickness. Expression of loricrin and keratin 5 in skin lesions was decreased following treatment with IL-36γ. Levels of IL-17A, interferon-γ, β-catenin and Dickkopf-related protein 1 were elevated in keratinocytes within psoriatic lesions following IL-36γ stimulation.ConclusionsTogether, these data showed that IL-36γ contribute to abnormal keratinocytes proliferation and keratinocyte-related proinflammatory cytokines, and suggest that IL-36γ may play an important role in the pathogenesis of psoriasis.

Evaluation of anti-psoriatic activity of selected phytochemicals on UV-induced psoriasis in mouse tail model

2020 ◽  
Vol 64 ◽  
pp. 123-128
Author(s):  
Jada Naga Lakshmi ◽  
A. Narendra Babu ◽  
Rama Rao Nadendla
Keyword(s):  
Disease Control ◽  
Ellagic Acid ◽  
Uv Light ◽  
Severity Index ◽  
Treated Group ◽  
Control Group ◽  
Standard Group ◽  
Significant Activity ◽  
Epidermal Thickness ◽  
Psoriasis Severity

Objectives: To evaluate anti-psoriatic activity of Phytochemicals on UV-Induced psoriasis in mouse tail model. Materials and Methods: Anti-psoriatic activity of selected phytochemicals on UV-Induced psoriasis in mouse tail model. The animals were dividing into 05 groups and each group contain 5 animals. Disease control group did not receive any treatment only exposure to UV-light, vehicle control treated with simple ointment, standard group treated with salicylic acid (1%w/w) ointment, remaining group are treated 1% and 2% selective phytochemical at two concentrations of ointment to topically on the tail skin. And the data were analysed using one way ANOVA followed by two-way ANOVA (Dunnett’s multiple comparisons test). Results: There was significant decrease in epidermal thickness (P < 0.05) as compared with control group. In 2% phytoconstituents has shown a significant reduction in the total epidermal thickness 8.4****±0.748, 7.6**±0.6781 and 8*±0.8366 in geraniol, glycyrrhizic acid and ellagic acid treated group, when compare to the disease induced animal, there was no lesion of Munro’s microabscess, capillary loop dilation along with elongation of rete ridges in the section of skin of rats. Psoriasis Severity Index was reduced in test treated groups as compared with that of disease control group. It was slowly reduced to 2nd week, totally (55-70%) reduction in PSI is observed at the time of third week of treatment period. Conclusion: The result of the study showed that the 2% of geraniol, ellagic acid, glycyrrhizicacid and hesperidin, exhibited significant activity on UV-induced psoriasis in rodents. The study implies that selected phytoconstituents are a promising research for further investigations to prove its anti-psoriatic activity.

Attenuation of Lung Inflammation and Fibrosis in Interferon- γ –Deficient Mice after Intratracheal Bleomycin

2001 ◽  
Vol 24 (5) ◽  
pp. 545-555 ◽  
Author(s):  
Edward S. Chen ◽  
Brian M. Greenlee ◽  
Marsha Wills-Karp ◽  
David R. Moller
Keyword(s):  
Lung Inflammation ◽  
Interferon Γ ◽  
Deficient Mice

scholarly journals Combination Treatment of Topical Imiquimod Plus Anti-PD-1 Antibody Exerts Significantly Potent Antitumor Effect

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3948
Author(s):  
Kazumasa Oya ◽  
Yoshiyuki Nakamura ◽  
Zhu Zhenjie ◽  
Ryota Tanaka ◽  
Naoko Okiyama ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Combination Therapy ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Antitumor Effect ◽  
Skin Lesions ◽  
Ifn Γ ◽  
Deficient Mice

The exact mechanisms of the imiquimod (IMQ)-induced antitumor effect have not been fully understood. Although both topical IMQ treatment and anti-PD-1 antibody may be used for primary skin lesions or skin metastases of various cancers, the efficacy of each monotherapy for these lesions is insufficient. Using a murine tumor model and human samples, we aimed to elucidate the detailed mechanisms of the IMQ-induced antitumor effect and analyzed the antitumor effect of combination therapy of topical IMQ plus anti-PD-1 antibody. Topical IMQ significantly suppressed the tumor growth of MC38 in wildtype mice. IMQ upregulated interferon γ (IFN-γ) expression in CD8+ T cells in both the lymph nodes and the tumor, and the antitumor effect was abolished in both Rag1-deficient mice and IFN-γ-deficient mice, indicating that IFN-γ produced by CD8+ T cells play a crucial role in the IMQ-induced antitumor effect. IMQ also upregulated PD-1 expression in T cells as well as PD-L1/PD-L2 expression in myeloid cells, suggesting that IMQ induces not only T-cell activation but also T-cell exhaustion by enhanced PD-1 inhibitory signaling. Combination therapy of topical IMQ plus anti-PD-1 antibody exerted a significantly potent antitumor effect when compared with each single therapy, indicating that the combination therapy is a promising therapy for the skin lesions of various cancers.

scholarly journals Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis

2021 ◽  
Author(s):  
Mariko Seishima ◽  
Yasuko Yamamoto ◽  
Masashi Sakurai ◽  
Rika Sakai ◽  
Kento Fujii ◽  
...  
Keyword(s):  
High Performance ◽  
Severity Index ◽  
Skin Lesions ◽  
Kynurenine Pathway ◽  
Psoriasis Area Severity Index ◽  
Systemic Inflammatory Disease ◽  
Cytokine Levels ◽  
Uninvolved Skin ◽  
Psoriasis Therapy ◽  
Hydroxyanthranilic Acid

Aim: Chronic inflammation is closely associated with tryptophan (TRP)-kynurenine (KYN) metabolic pathway. However, TRP-KYN pathway has not been fully elucidated in psoriasis, a systemic inflammatory disease with skin lesions and extracutaneous manifestations. Herein, we studied comprehensively serum profiles of TRP-KYN pathway metabolites in psoriatic patients (PSOs) to clarify the involvement of this pathway in the pathophysiology of psoriasis and to evaluate serum biomarkers reflecting systemic inflammation in PSOs. Methods: The concentrations of main TRP metabolites, TRP, KYN, 3-hydroxykynurenine (3HK), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), and anthranilic acid (AA), were determined by high-performance liquid chromatography in the sera from 65 PSOs and 35 healthy controls (HCs). The levels of these metabolites and the ratios of metabolites were compared between these subjects. The correlations between these values and the psoriasis area severity index (PASI) scores were analyzed. Skin samples from PSOs and HCs were subjected to immunohistochemical staining for kynureninase. Cytokine concentrations were comprehensively measured in the same samples and the correlations between the cytokine levels and TRP-KYN pathway metabolite levels were examined. Results: Serum TRP, KYN, and KYNA concentrations were lower and the 3HAA concentrations were higher in PSOs than in HCs. The ratios of 3HK/KYN, 3HAA/3HK, and 3HK/AA were higher in PSOs than in HCs. The AA levels and the ratio of AA/KYN were weakly positively correlated, and TRP, KYNA, and 3HK levels and the ratios of KYNA/KYN and 3HAA/AA were weakly negatively correlated with the PASI scores. The AA, KYN, and KYNA levels were positively correlated with the interferon gamma-induced protein 10 (IP-10) concentrations. Kynureninase expression was enhanced in the epidermis, both involved and uninvolved skin. Conclusions: Serum profiles of TRP-KYN pathway metabolites differed between PSOs and HCs. TRP-KYN pathway-associated processes, including kynureninase activation, may be involved in the pathogenesis of psoriasis, and thus serve as targets for psoriasis therapy.

scholarly journals Prospective, Comparative Clinical Pilot Study of Cold Atmospheric Plasma Device in the Treatment of Atopic Dermatitis

2021 ◽  
Author(s):  
Young Jae Kim ◽  
Dong Jun Lim ◽  
Mi Young Lee ◽  
Woo Jin Lee ◽  
Sung Eun Chang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Pilot Study ◽  
Severity Index ◽  
Skin Lesions ◽  
Treated Group ◽  
Atmospheric Plasma ◽  
Clinical Severity ◽  
Control Treatment ◽  
Cold Atmospheric Plasma ◽  
Plasma Device

Abstract Introduction: Cold atmospheric plasma generates free radicals through the ionization of air at room temperature. Its effect and safety profile in patients with atopic dermatitis have not been evaluated prospectively.Objective: We aimed to investigate the effect and safety of cold atmospheric plasma in patients with atopic dermatitis with a prospective pilot study.Methods: Cold atmospheric plasma treatment or sham control treatment were applied respectively in randomly assigned and symmetric skin lesions. Three treatment sessions were performed at weeks 0, 1, and 2. Clinical severity indices were assessed at weeks 0, 1, 2, and 4 after treatment. Additionally, the microbial characteristics of the lesions before and after treatments were analyzed.Results: We included 22 patients with mild to moderate atopic dermatitis presented with symmetric lesions. We found that cold atmospheric plasma can alleviate the clinical severity of atopic dermatitis. Modified atopic dermatitis antecubital severity and eczema area and severity index score were significantly decreased in the treated group. Furthermore, scoring of atopic dermatitis score and pruritic visual analog scales significantly improved. In microbiome analysis revealed significantly reduced proportion of Staphylococcus aureus in the treated group.Conclusion: Cold atmospheric plasma can significantly improve mild and moderate atopic dermatitis without safety issues.

scholarly journals Therapeutic Efficacies of Artemisia capillaris Extract Cream Formulation in Imiquimod-Induced Psoriasis Models

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Song Yi Lee ◽  
Suyeong Nam ◽  
Sungyun Kim ◽  
Ja Seong Koo ◽  
In Kee Hong ◽  
...  
Keyword(s):  
Skin Lesions ◽  
The Other ◽  
Epidermal Thickness ◽  
Artemisia Capillaris ◽  
Cream Formulation ◽  
Cumulative Score ◽  
Intracellular Adhesion Molecule ◽  
Psoriasis Therapy ◽  
Hematoxylin And Eosin ◽  
Hematoxylin And Eosin Staining

A cream formulation containing Artemisia capillaris (AC) extract (ACE) was developed for psoriasis therapy. Although ACE can be dissolved in organic solvents, its topical application is restricted because of toxicities. Therefore, a cream formulation was developed for the convenient and safe local application of ACE on skin lesions. The antipsoriatic properties of the ACE cream were evaluated using an imiquimod- (IMQ-) induced psoriasis-like mouse model. In psoriasis-like mouse models, the cumulative score (redness, thickness, and scaling) of the IMQ + ACE cream group was significantly lower than those of the other groups on day 4 (p < 0.05). The results of the hematoxylin and eosin staining of skin tissues revealed that the epidermal thickness value of the IMQ + ACE cream group was significantly lower than those of the other experimental groups (p < 0.05). The expression level of intracellular adhesion molecule-1 (ICAM-1), which indicates the leukocyte infiltration into the skin and subsequent interactions with keratinocytes, was also lower in the IMQ + ACE cream group than in the IMQ group. These results indicate that ACE cream formulation could be used safely and conveniently for psoriasis treatment.

Increased Fetal and Extramedullary Hematopoiesis in Fas-Deficient C57BL/6-lpr/lpr Mice

Blood ◽  
1999 ◽  
Vol 94 (8) ◽  
pp. 2613-2621 ◽  
Author(s):  
Elke Schneider ◽  
Géraldine Moreau ◽  
Anne Arnould ◽  
Florence Vasseur ◽  
Naushad Khodabaccus ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Bone Marrow Cells ◽  
Extramedullary Hematopoiesis ◽  
Interferon Γ ◽  
Regulatory Function ◽  
Fetal Life ◽  
Adult Mice ◽  
Colony Forming Units ◽  
Immature Myeloid Cells ◽  
Deficient Mice

In this study, we examined the consequences of Fas deficiency on hematopoiesis in C57BL/6-lpr/lpr mice. We found a striking extramedullary increase in hematopoietic progenitor cells, comprising erythroid and nonerythroid lineages alike. These modifications preceded the lymphadenopathy, because early progenitors (colony-forming units-spleen [CFU-S] day 8) were already augmented in day-18 fetal livers of the lpr phenotype. Three weeks after birth, CFU-S increased in peripheral blood and spleen and colony-forming cells (CFU-C) began to accumulate 1 to 3 weeks later. Extramedullary myelopoiesis augmented progressively in Fas-deficient mice, reaching a maximum within 6 months. By then, mature and immature myeloid cells had infiltrated the spleen, the liver, and the peritoneal cavity. Similar changes occurred in C57BL/6-gld/gld mice, indicating that they resulted from Fas/FasL interactions. Medullary hematopoiesis was not significantly modified in adult mice of either strain. Yet, the incidence of CFU-S decreased after Fas cross-linking on normal bone marrow cells in the presence of interferon γ, consistent with a regulatory function of Fas/FasL interactions in early progenitor cell development. These data provide evidence that Fas deficiency can affect hematopoiesis both during adult and fetal life and that these modifications occur independently from other pathologies associated with the lpr phenotype.

Inhibition of poly(ADP-ribose) polymerase attenuates inflammation in a model of chronic colitis

2000 ◽  
Vol 279 (3) ◽  
pp. G641-G651 ◽  
Author(s):  
Humberto B Jijon ◽  
Thomas Churchill ◽  
David Malfair ◽  
Andreas Wessler ◽  
Laurence D Jewell ◽  
...  
Keyword(s):  
Intestinal Permeability ◽  
Proinflammatory Cytokine ◽  
Time Course ◽  
Nitrosative Stress ◽  
Tissue Injury ◽  
Parp Inhibitor ◽  
Interferon Γ ◽  
Cytokine Release ◽  
Energy Status ◽  
Deficient Mice

Crohn's disease is a chronic disease characterized by oxidant-induced tissue injury and increased intestinal permeability. A consequence of oxidative damage is the accumulation of DNA strand breaks and activation of poly(ADP-ribose) polymerase (PARP), which subsequently catalyzes ADP-ribosylation of target proteins. In this study, we assessed the role of PARP in the colitis seen in interleukin (IL)-10 gene-deficient mice. IL-10 gene-deficient mice demonstrated significant alterations in colonic cellular energy status in conjunction with increased permeability, proinflammatory cytokine release, and nitrosative stress. After 14 days of treatment with the PARP inhibitor 3-aminobenzamide, IL-10 gene-deficient mice demonstrated normalized colonic permeability; reduced tumor necrosis factor-α and interferon-γ secretion, inducible nitric oxide synthase expression, and nitrotyrosine levels; and significantly attenuated inflammation. Time course studies demonstrated that 3-aminobenzamide rapidly altered cellular metabolic activity and decreased cellular lactate levels. This was associated with normalization of colonic permeability and followed by a downregulation of proinflammatory cytokine release. Our data demonstrate that inhibition of PARP activity results in a marked improvement of colonic inflammatory disease and a normalization of cellular metabolic function and intestinal permeability.

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