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 Basophil Recruitment to Skin Lesions of Patients with Systemic Lupus Erythematosus Mediated by CCR1 and CCR2

2017 ◽  
Vol 43 (2) ◽  
pp. 832-839 ◽  
Author(s):  
Qingjun Pan ◽  
Yongmin Feng ◽  
Yanxia Peng ◽  
Hongjiu Zhou ◽  
Zhenzhen Deng ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Migration Rate ◽  
Skin Diseases ◽  
Normal Skin ◽  
Flow Cytometric Analysis ◽  
Skin Lesions ◽  
Skin Tissue ◽  
Systemic Lupus

Background/Aims: Basophils have been reported to infiltrate skin lesions in various skin diseases, but not in systemic lupus erythematosus (SLE). This study investigated basophil infiltration in SLE and its mechanism. Methods: Twenty newly diagnosed SLE patients and twenty healthy controls were enrolled. Nine SLE patients underwent skin biopsies. Flow cytometric analysis the phenotype of peripheral basophils and their migration rate toward RANTES and MCP-1 were analyzed with the transwell culture system, also the expression of these two chemokines in skin tissue were analyzed with immunohistochemistry. Results: Increased activation and decreased numbers of peripheral basophils were observed in SLE patients compared with controls. Basophil migration into skin lesions of SLE patients were observed, but not in normal skin tissue. This migration was related to the upregulation of chemokine receptors CCR1 and CCR2 on basophils. In vitro studies showed that migration rate toward RANTES and MCP-1 increased significantly in basophils from SLE patients compared with those from controls. Consistently, high levels of RANTES and MCP-1 expression were observed in skin lesions from SLE patients but not in normal skin tissue. Conclusion: Basophil recruitment to skin lesions of SLE patients mediated by CCR1 and CCR2, which may contribute to tissue damage in SLE.

scholarly journals ZnO NPs delay the recovery of psoriasis-like skin lesions through promoting inflammation and keratinocyte apoptosis via nuclear translocation of phosphorylated NF-κB p65 and cysteine deficiency

2020 ◽  
Author(s):  
Xuan Lai ◽  
Menglei Wang ◽  
Yixia Zhu ◽  
Xiaoli Feng ◽  
Huimin Liang ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Nuclear Translocation ◽  
Normal Skin ◽  
Redox Homeostasis ◽  
Skin Lesions ◽  
Zno Nps ◽  
Inflammatory Skin Diseases ◽  
Tnf Α ◽  
Jnk Inhibitors

Abstract Background This study aimed to confirm the safety and risk of applying zinc oxide nanoparticles (ZnO NPs) to pathological skin, such as psoriasis-like skin. The majority of previous studies confirmed the safety of applying ZnO NPs to normal skin. However, we know very little about the risks of using sunscreen, cosmetics and topical drugs containing ZnO NPs for individuals with skin diseases. In addition, some studies claimed that ZnO NPs can penetrate normal or pathological skin, and ZnO NPs have frequently been reported to have proinflammatory and lethal effects in vitro. Therefore, it is necessary to evaluate the safety of applying ZnO NPs to pathological skin. Results ZnO NPs passed through gaps between keratinocytes and entered stratum basale of epidermis and dermis in imiquimod (IMQ)-induced psoriasis-like skin lesions. Application of a ZnO NP-containing suspension for 3 connective days delayed the healing of the epidermal barrier; increased the expression levels of inflammatory cytokines; promoted keratinocyte apoptosis and disturbed redox homeostasis. In vitro, ZnO NPs promoted TNF-α, IL-1β and IL-6 secretion and apoptosis of recombinant-human-TNF-α-stimulated HaCaT cells. NF-κB, ERK, p38 and JNK inhibitors blocked ZnO NP-induced inflammation. JSH-23, an inhibitor of the nuclear translocation of p-NF-κB p65, and NAC, an acetylated precursor of L-cysteine, not only inhibited the ZnO NP-induced inflammation but also inhibited apoptosis and cysteine deficiency. Neither erastin nor RSL3 induced p-NF-κB p65 nuclear translocation, but they did reduce cysteine biosynthesis. Additionally, ferropstatin-1, an inhibitor of lipid peroxidation, partially rescued ZnO NP-induced decreases in cell viability and cysteine content. Conclusions ZnO NPs delay the recovery of psoriasis-like skin lesions through promoting inflammation and keratinocyte apoptosis via the nuclear translocation of phosphorylated NF-κB p65 and cysteine deficiency. This work reminds the public that ZnO NPs are not safe for pathological skin, especially in inflammatory skin diseases such as psoriasis, and has revealed a partial mechanism by which ZnO NPs delay the recovery of pathological skin, promoting the appropriate use of ZnO NPs.

scholarly journals Three Constituents of Moringa oleifera Seeds Regulate Expression of Th17-Relevant Cytokines and Ameliorate TPA-Induced Psoriasis-Like Skin Lesions in Mice

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3256 ◽  
Author(s):  
Nuan Ma ◽  
Qin Tang ◽  
Wan-Ting Wu ◽  
Xin-An Huang ◽  
Qin Xu ◽  
...  
Keyword(s):  
Moringa Oleifera ◽  
Skin Diseases ◽  
Critical Role ◽  
Folk Medicine ◽  
Skin Lesions ◽  
Keratinocyte Differentiation ◽  
Therapeutic Application ◽  
Differentiation Markers

As a folk medicine, Moringa oleifera L. is used effectively to treat inflammatory conditions and skin diseases. However, its mechanism of action is not well understood, limiting its medical use. We isolated and identified three compounds, namely niazirin, marumoside A and sitosterol-3-O-β-d-glucoside, from the seeds of Moringa oleifera, and studied their effects on the expression of Th17-relevant cytokines (IL-12/IL-23 p40, IL-17A, IL-22 and IL-23 p19) using lipopolysaccharide-stimulated THP-1 cells. Additionally, as Th17 plays a critical role in the pathogenesis of psoriasis, we used a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced psoriasis-like skin lesion mouse model to study their potential therapeutic application in vivo. The compounds suppressed the expression of IL-12/IL-23 p40, IL-17A, IL-22 and IL-23 p19 in vitro, and in vivo they ameliorated psoriasis-like skin lesions, decreased IL-17A mRNA expression, and increased the expression of keratinocyte differentiation markers. To our knowledge, this is the first report regarding the mechanism and therapeutic application of Moringa oleifera seeds to treat psoriasis-like lesions in vivo.

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.

Aquaporin 3 (AQP-3) modulatory effects of an herbal formulated cream in the management of skin psoriasis

2016 ◽  
Vol 5 (07) ◽  
pp. 4667
Author(s):  
Harsha M. R.* ◽  
Baidyanath Mishra ◽  
Chaithra C. S. ◽  
Vivekananda Ramana
Keyword(s):  
Normal Skin ◽  
Water Channel ◽  
Basal Layer ◽  
Skin Lesions ◽  
Skin Hydration ◽  
Psoriatic Skin ◽  
Test Substance ◽  
Mrna Levels ◽  
Aquaporin 3

Aquaporins form a large family of integral, transmembrane water channel proteins that mainly function in transporting water over cellular membranes. Amongst aquaporins, aquaporin-3 (AQP-3) is the predominant skin aquaporin which is localised in the basal layer keratinocytes of epidermis in normal skin, and is found to be important in maintaining balanced skin hydration. In addition, several clinical studies have demonstrated reduced AQP-3 expression in cases of psoriasis, suggesting a strong relationship between AQP-3 expression levels and skin hydration/epidermal water loss in psoriatic skin. In scope of this, the potential to manipulate AQP-3 levels by skin care products designed to address psoriatic skin problems gains pharmaceutical attraction. Therefore, we examined the effects of InnoVision’s Psoriderm cream on AQP-3 expression in keratinocytic cell culture model in vitro. AQP-3 expression was found to be significantly increased upon treating keratinocytes with the study material. Test substance at concentrations, 350 and 700 µg/mL increased AQP-3 mRNA levels by 0.03 and 0.07 folds, compared to untreated control cells. In summary, it could be illustrated that using InnoVision’s Psoriderm in psoriasis care can up regulate AQP-3 expression in psoriatic skin, and thus may play a functional in bettering skin conditions in psoriatic skin lesions. 

Role of specific probiotics in skin diseases: new insights from in vitro investigation

2021 ◽  
Author(s):  
Diletta Squarzanti ◽  
Paola Zanetta ◽  
Marcello Manfredi ◽  
Margherita Ormelli ◽  
Angela Amoruso ◽  
...  
Keyword(s):  
Skin Diseases ◽  
In Vitro Investigation

scholarly journals PCR-based identification of Mycobacterium murphy causing Canine Leproid Granuloma Syndrome in Niterói, southeast Brazil - case report

2018 ◽  
Vol 70 (6) ◽  
pp. 1699-1702
Author(s):  
M.A.A. Pereira ◽  
V. Nowosh ◽  
P.N. Suffys ◽  
G.B. Queiroz ◽  
K.M.O. Silva ◽  
...  
Keyword(s):  
Molecular Identification ◽  
Rio De Janeiro ◽  
Skin Diseases ◽  
Pcr Amplification ◽  
Infectious Agent ◽  
Skin Lesions ◽  
Molecular Techniques ◽  
Hsp65 Gene ◽  
Janeiro State

ABSTRACT Canine Leproid Granuloma Syndrome (CLGS), also known as canine leprosy, is a cutaneous nodular infectious disease caused by Mycobacterium sp.. Despite being reported worldwide, it is still quite unknown and underdiagnosed. Diagnosis may be achieved by cytopathology or histopathology of skin lesions, but identification of the infectious agent is complex, since bacterial in vitro growth is not possible, relying upon molecular techniques such as PCR to confirm Mycobacterium DNA in the sample. We report a CLGS case in Niteroi, Rio de Janeiro state, Brazil, diagnosed by cytopathology and submitted to molecular identification of the agent. PCR amplification of hsp65 gene was performed and revealed 100% genetic homology to M. murphy strain. This is the first CLGS report with molecular identification in Rio de Janeiro state, and this finding should raise awareness about CLGS as a differential diagnosis among granulomatous skin diseases in this region.

scholarly journals The Role of MicroRNAs in Epidermal Barrier

2020 ◽  
Vol 21 (16) ◽  
pp. 5781
Author(s):  
Ai-Young Lee
Keyword(s):  
Cell Adhesion ◽  
Critical Role ◽  
Keratinocyte Differentiation ◽  
Epidermal Barrier ◽  
Barrier Integrity ◽  
Skin Lipids ◽  
Differentiation And Proliferation ◽  
The Impact ◽  
Cell Cell

MicroRNAs (miRNAs), which mostly cause target gene silencing via transcriptional repression and degradation of target mRNAs, regulate a plethora of cellular activities, such as cell growth, differentiation, development, and apoptosis. In the case of skin keratinocytes, the role of miRNA in epidermal barrier integrity has been identified. Based on the impact of key genetic and environmental factors on the integrity and maintenance of skin barrier, the association of miRNAs within epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids is reviewed. The critical role of miRNAs in the epidermal barrier extends the use of miRNAs for control of relevant skin diseases such as atopic dermatitis, ichthyoses, and psoriasis via miRNA-based technologies. Most of the relevant miRNAs have been associated with keratinocyte differentiation and proliferation. Few studies have investigated the association of miRNAs with structural proteins of corneocytes and cornified envelopes, cell–cell adhesion, and skin lipids. Further studies investigating the association between regulatory and structural components of epidermal barrier and miRNAs are needed to elucidate the role of miRNAs in epidermal barrier integrity and their clinical implications.

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