scholarly journals Myeloperoxidase Inhibition Ameliorates Plaque Psoriasis in Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1338
Author(s):  
Savannah D. Neu ◽  
Anna Strzepa ◽  
Dustin Martin ◽  
Mary G. Sorci-Thomas ◽  
Kirkwood A. Pritchard, Jr. ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Plaque Psoriasis ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
Autoimmune Response ◽  
Psoriatic Skin ◽  
Imiquimod Cream ◽  
Current Therapies ◽  
Study Support

Plaque psoriasis is a common inflammatory condition of the skin characterized by red, flaking lesions. Current therapies for plaque psoriasis target many facets of the autoimmune response, but there is an incomplete understanding of how oxidative damage produced by enzymes such as myeloperoxidase contributes to skin pathology. In this study, we used the Aldara (Imiquimod) cream model of plaque psoriasis in mice to assess myeloperoxidase inhibition for treating psoriatic skin lesions. To assess skin inflammation severity, an innovative mouse psoriasis scoring system was developed. We found that myeloperoxidase inhibition ameliorated psoriasis severity when administered either systemically or topically. The findings of this study support the role of oxidative damage in plaque psoriasis pathology and present potential new therapeutic avenues for further exploration.

The role of telomerase activity in psoriatic skin lesions

2007 ◽  
Vol 68 (5) ◽  
pp. 1093-1095 ◽  
Author(s):  
Davor Jurisic ◽  
Ivan Kirin ◽  
Domagoj Rabic ◽  
Bojan Dojcinovic ◽  
Miran Coklo ◽  
...  
Keyword(s):  
Skin Lesions ◽  
Telomerase Activity ◽  
Psoriatic Skin

scholarly journals Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation

2007 ◽  
Vol 204 (11) ◽  
pp. 2603-2614 ◽  
Author(s):  
Hal Blumberg ◽  
Huyen Dinh ◽  
Esther S. Trueblood ◽  
James Pretorius ◽  
David Kugler ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Inflammatory Cell ◽  
Family Members ◽  
Skin Inflammation ◽  
Antagonistic Activity ◽  
Psoriatic Skin ◽  
Inflammatory Cell Infiltrate ◽  
Skin Abnormalities

The interleukin (IL)-1 family members IL-1α, -1β, and -18 are potent inflammatory cytokines whose activities are dependent on heterodimeric receptors of the IL-1R superfamily, and which are regulated by soluble antagonists. Recently, several new IL-1 family members have been identified. To determine the role of one of these family members in the skin, transgenic mice expressing IL1F6 in basal keratinocytes were generated. IL1F6 transgenic mice exhibit skin abnormalities that are dependent on IL-1Rrp2 and IL-1RAcP, which are two members of the IL-1R family. The skin phenotype is characterized by acanthosis, hyperkeratosis, the presence of a mixed inflammatory cell infiltrate, and increased cytokine and chemokine expression. Strikingly, the combination of the IL-1F6 transgene with an IL1F5 deficiency results in exacerbation of the skin phenotype, demonstrating that IL-1F5 has antagonistic activity in vivo. Skin from IL1F6 transgenic, IL1F5−/− pups contains intracorneal and intraepithelial pustules, nucleated corneocytes, and dilated superficial dermal blood vessels. Additionally, expression of IL1RL2, -1F5, and -1F6 is increased in human psoriatic skin. In summary, dysregulated expression of novel agonistic and antagonistic IL-1 family member ligands can promote cutaneous inflammation, revealing potential novel targets for the treatment of inflammatory skin disorders.

scholarly journals Staphylococcus aureus lipoproteins promote abscess formation in mice, shielding bacteria from immune killing

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Majd Mohammad ◽  
Manli Na ◽  
Zhicheng Hu ◽  
Minh-Thu Nguyen ◽  
Pradeep Kumar Kopparapu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
Lesion Size ◽  
Abscess Formation ◽  
Skin Infections ◽  
Human Immune System ◽  
Immune Evasion Mechanism ◽  
Human Immune

AbstractDespite being a major bacterial factor in alerting the human immune system, the role of Staphylococcus aureus (S. aureus) lipoproteins (Lpp) in skin infections remains largely unknown. Here, we demonstrated that subcutaneous injection of S. aureus Lpp led to infiltration of neutrophils and monocytes/macrophages and induced skin lesions in mice. Lipid-moiety of S. aureus Lpp and host TLR2 was responsible for such effect. Lpp-deficient S. aureus strains exhibited smaller lesion size and reduced bacterial loads than their parental strains; the altered phenotype in bacterial loads was TLR2-independent. Lpp expression in skin infections contributed to imbalanced local hemostasis toward hypercoagulable state. Depletion of leukocytes or fibrinogen abrogated the effects induced by Lpp in terms of skin lesions and bacterial burden. Our data suggest that S. aureus Lpp induce skin inflammation and promote abscess formation that protects bacteria from innate immune killing. This suggests an intriguing bacterial immune evasion mechanism.

scholarly journals Rapamycin Alleviates 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Aggravated Dermatitis in Mice with Imiquimod-Induced Psoriasis-Like Dermatitis by Inducing Autophagy

2021 ◽  
Vol 22 (8) ◽  
pp. 3968
Author(s):  
Hye Ran Kim ◽  
Jin Cheol Kim ◽  
Seok Young Kang ◽  
Hye One Kim ◽  
Chun Wook Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
Psoriatic Skin ◽  
Related Factor ◽  
Related Factors ◽  
Tetrachlorodibenzo P Dioxin

Recently, the mTOR signaling has emerged as an important player in the pathogenesis of psoriasis. We previously found that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced psoriatic skin inflammation was related to the inhibition of autophagy in keratinocytes. However, the effects and detailed molecular mechanisms of the mTOR inhibitor rapamycin and TCDD on psoriasis in vivo remain to be elucidated. In this study, we aimed to evaluate the effects of rapamycin and TCDD on skin lesions in imiquimod (IMQ)-induced psoriasis using a mouse model. TCDD aggravated skin inflammation in an IMQ-induced psoriatic mouse model. Furthermore, TCDD increased the expression of aryl hydrocarbon receptor (AHR), CYP1A1, proinflammatory cytokines, oxidative stress markers (NADPH oxidase (Nox) 2, Nox4), and phosphorylated P65NF-ĸB, whereas the expression of autophagy-related factors and the antioxidant marker nuclear factor-erythroid 2-related factor 2 (NRF2) decreased. Rapamycin reduced the aggravated skin inflammation induced by TCDD and restored TCDD-induced autophagy suppression and the increase of AHR expression, oxidative stress, and inflammatory response in the skin lesions of a psoriatic mouse model. In conclusion, we demonstrated that rapamycin alleviates TCDD-induced aggravated dermatitis in mice with imiquimod-induced psoriasis-like dermatitis through AHR and autophagy modulation.

scholarly journals miR-155 Contributes to Normal Keratinocyte Differentiation and Is Upregulated in the Epidermis of Psoriatic Skin Lesions

2020 ◽  
Vol 21 (23) ◽  
pp. 9288
Author(s):  
Lucian Beer ◽  
Polina Kalinina ◽  
Martin Köcher ◽  
Maria Laggner ◽  
Markus Jeitler ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Normal Skin ◽  
Skin Lesions ◽  
Keratinocyte Differentiation ◽  
Psoriatic Skin ◽  
Bioinformatics Analyses ◽  
Epidermal Barrier ◽  
Barrier Formation

The role of microRNAs (miRNAs) during keratinocyte (KC) differentiation and in skin diseases with epidermal phenotypes has attracted strong interest over the past few years. However, combined mRNA and miRNA expression analyses to elucidate the intricate mRNA–miRNA networks of KCs at different stages of differentiation have not been performed yet. In the present study, we investigated the dynamics of miRNA and mRNA expression during KC differentiation in vitro and in normal and psoriatic epidermis. While we identified comparable numbers of up- and downregulated mRNAs (49% and 51%, respectively), miRNAs were predominantly upregulated (76% vs 24%) during KC differentiation. Further bioinformatics analyses suggested an important inhibitory role for miR-155 in KC differentiation, as it was repressed during KC differentiation in normal skin but strongly upregulated in the epidermis of psoriatic skin lesions. Mimicking the inflammatory milieu of psoriatic skin in vitro, we could show that the pro-inflammatory cytokines IL17, IL1β and INFγ synergistically upregulated miR-155 expression in KCs. Forced over-expression of miR-155 in human in vitro skin models specifically reduced the expression of loricrin (LOR) in KCs, indicating that miR-155 interferes with the establishment of a normal epidermal barrier. Together, our data indicate that downregulation of miR-155 during KC differentiation is a crucial step for epidermal barrier formation. Furthermore, its strong upregulation in psoriatic lesions suggests a contributing role of miR-155 in the altered keratinocyte differentiation observed in psoriasis. Therefore, miR-155 represents as a potential target for treating psoriatic skin lesions.

scholarly journals PSORIASIS IN HIV-INFECTED PATIENTS: CLINICAL AND LABORATORY EVALUATION, APPROACHES TO THERAPY

2017 ◽  
Vol 20 (4) ◽  
pp. 227-231
Author(s):  
Evgeny Yu. Evdokimov ◽  
A. V Sundukov
Keyword(s):  
Practical Interest ◽  
Skin Lesions ◽  
Laboratory Evaluation ◽  
Psoriatic Skin ◽  
Inflammatory Reactions ◽  
Treatment Regimens ◽  
Before And After ◽  
Index Of Severity ◽  
Evaluation Approaches

Clinical and laboratory evaluation of the effectiveness of therapy of psoriasis vulgaris in 78 HIV-infected patients using the two treatment regimens is presented. Peculiarities of clinical course of psoriasis depending on the number of CD4+lymphocytes in the peripheral blood are shown. Histological and histochemical studies of biopsy samples from psoriatic skin lesions and apparently healthy skin in 15 people were performed. The dynamics before and after treatment of CD4+ and CD8+ lymphocytes in biopsies of skin and blood, their relationship with the index of severity of psoriasis (PASI) are presented. This study is of theoretical and practical interest in understanding the value and role of CD4+ and CD8+ lymphocytes in the formation of inflammatory reactions in the skin of patients with psoriasis as a possible option for treatment of psoriasis in HIV-infected patients.

scholarly journals RNA-antimicrobial peptide LL-37 complexes fuel a TLR- and NET-mediated inflammatory cycle of neutrophil activation in psoriasis

2018 ◽  
Author(s):  
Franziska Herster ◽  
Zsofia Bittner ◽  
Sabine Dickhöfer ◽  
David Eise ◽  
Tatjana Eigenbrod ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Intervention Strategy ◽  
Skin Lesions ◽  
Neutrophil Extracellular Trap ◽  
Psoriatic Skin ◽  
Bacterial Rna ◽  
Human Pmns ◽  
Inflammatory Autoimmune Disease

AbstractPsoriasis is an inflammatory autoimmune disease characterized by skin lesions showing strong neutrophil (PMN) infiltration and high levels of the antimicrobial peptide, LL37, but the role of PMNs in this context remains unclear. We here show that primary human PMNs, especially PMNs from psoriasis patients, not only respond via TLR8 to human and bacterial RNA in complexed with LL37 by cytokine-, chemokine- and neutrophil extracellular trap (NET)-release; they also actively release additional RNA and LL37 in response to stimulation by the same complex and both RNA and LL37 were found to be highly abundant in psoriatic skin. Moreover, RNA-LL37-induced NETs propagated PMN activation and could thus fuel a PMN-mediated and self-sustaining inflammatory loop that may represent an unexpected early initiator or amplifying event in psoriasis. Given that TLR inhibitory oligodeoxynucleotides prevented the cytokine production and NETosis of PMNs by RNA-LL37 complexes in vitro, our study also highlights TLR blockade as a potential therapeutic intervention strategy in psoriasis.SummaryHuman and bacterial RNA in complex with LL37 activates neutrophils via TLR8 to release cytokines, chemokines and neutrophil extracellular traps (NETs). NETs and neutrophil-rich areas in psoriatic skin contain RNA and LL37, suggesting RNA-LL37 may fuel a PMN-mediated and self-sustaining inflammatory cycle in psoriasis.

scholarly journals Pellino 1 Communicates Intercellular Signaling in Chronic Skin Inflammatory Microenvironment

2018 ◽  
Author(s):  
Suhyeon Kim ◽  
Seoyoon Bae ◽  
Jihyun Park ◽  
Geun-Hyoung Ha ◽  
Kyungrim Hwang ◽  
...  
Keyword(s):  
Skin Inflammation ◽  
Skin Lesions ◽  
Psoriatic Skin ◽  
Intercellular Signaling ◽  
Multisystem Disease ◽  
Signaling Mechanism ◽  
Inflammatory Microenvironment ◽  
Systemic Signaling ◽  
Ubiquitin E3 Ligase ◽  
Chronic Skin

AbstractChronic skin inflammation including psoriasis is a multisystem disease, affecting more than 5% of the general population. Here we show that Pellino 1 (Peli1), a signal-responsive ubiquitin E3 ligase, is highly up-regulated in human psoriatic skin lesions and that increased Peli1 expression correlates with the immunopathogenesis of psoriasis-like chronic skin inflammatory disease. Interestingly, Peli1 directly interacts with interferon regulatory factor 4 (IRF4, a transcription factor that plays pivotal roles in proliferation and cytokine production) and induces lysine 63-mediated ubiquitination. Peli1-mediated IRF4 ubiquitination appears to be a common systemic signaling mechanism shared by lesional keratinocytes, dendritic cells, macrophages, and T cells, generating a feedback relationship between keratinocyte and Th17 cell responses. Conversely, inhibition of Peli1 interferes with IRF4 induction and attenuates immunopathogenic signaling in the psoriasis. In summary, Peli1-mediated ubiquitination is a common immunopathogenic intercellular signaling in psoriasis-like chronic skin inflammatory microenvironment. Thus, targeting Peli1 could be used as a potential strategy for psoriasis treatment.

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