MicroRNA-125a Correlates with Decreased Psoriasis Severity and Inflammation and Represses Keratinocyte Proliferation

Dermatology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Fang Su ◽  
Liang Jin ◽  
Wei Liu
Keyword(s):  
Severity Index ◽  
Skin Tissue ◽  
Hacat Cells ◽  
Tissue Samples ◽  
Keratinocyte Proliferation ◽  
Lesional Skin ◽  
High Area ◽  
Tnf Α ◽  
Severity Index Score ◽  
Factor Α

Background: Psoriasis has a complex etiology related to inflammation and dysregulated immune system. MicroRNA (miR)-125a is a miRNA intimately related to inflammation and immunity; therefore, we presumed that it might play a role in the pathogenesis of psoriasis. This study aimed to investigate the correlation of miR-125a with disease severity and inflammation in psoriasis patients, and the effect of miR-125a on proliferation, apoptosis as well as its target signaling pathway in keratinocytes. Methods: Sixty psoriasis patients were consecutively recruited, then lesional and non-lesional skin tissue samples were collected. miR-125a in lesional and non-lesional skin tissues, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 mRNA expressions in lesional skin tissues were detected. Then, miR-125a overexpression, control overexpression, miR-125a knockdown and control knockdown plasmids were transfected into HaCaT cells. Subsequently, cell proliferation, apoptosis, IL-23R, JAK2, and STAT3 expressions were assessed. Results: miR-125a was reduced in lesional skin tissue compared with non-lesional skin tissue (p < 0.001), and it distinguished lesional skin tissue from non-lesional skin tissue with a high area under curve of 0.917 (95% CI 0.866–0.968). Negative association of miR-125a in lesional skin tissue with lesional body surface area (p = 0.037) and psoriasis area and severity index score (p < 0.001) was found. Additionally, miR-125a was negatively correlated with TNF-α (p = 0.001), IL-1β (p = 0.014), and IL-17 (p = 0.003) in lesional skin tissue. In cellular experiments, miR-125a overexpression inhibited proliferation and promoted apoptosis, while miR-125a knockdown enhanced proliferation and repressed apoptosis in HaCaT cells. Additionally, miR-125a negatively regulated the IL-23R/JAK2/STAT3 pathway in HaCaT cells. Conclusion: miR-125a could facilitate the disease monitoring and probably has the potential to be a therapeutic target in psoriasis.

scholarly journals Expression of miR-135b in Psoriatic Skin and Its Association with Disease Improvement

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1603 ◽  
Author(s):  
Pablo Chicharro ◽  
Pedro Rodríguez-Jiménez ◽  
Mar Llamas-Velasco ◽  
Nuria Montes ◽  
Ancor Sanz-García ◽  
...  
Keyword(s):  
Severity Index ◽  
Psoriatic Skin ◽  
Local Inflammatory Response ◽  
Lesional Skin ◽  
Basal Expression ◽  
Severity Index Score ◽  
Residual Lesions ◽  
Generation Sequencing ◽  
Additional Sample ◽  
Skin Samples

miRNAs have been associated with psoriasis since just over a decade. However, we are far from a complete understanding of their role during the development of this disease. Our objective was to characterize the cutaneous expression of miRNAs not previously described in psoriasis, the changes induced following the treatment with biologicals and their association with disease improvement. Next generation sequencing was performed from five skin samples from psoriasis patients (lesional and non-lesional skin) and five controls, and from this cohort, 12 microRNAs were selected to be analyzed in skin samples from 44 patients with plaque psoriasis. In 15 patients, an additional sample was obtained after three months of biological treatment. MiR-9-5p, miR-133a-3p and miR-375 were downregulated in the lesional skin of psoriasis patients. After treatment, expression of miR-133a-3p, miR-375, miR-378a and miR-135b in residual lesions returned towards the levels observed in non-lesional skin. The decrease in miR-135b levels after treatment with biologics was associated with both the improvement of patients evaluated through Psoriasis Area and Severity Index score and the decrease in local inflammatory response. Moreover, basal expression of miR-135b along with age was associated with the improvement of psoriasis, suggesting its possible usefulness as a prognostic biomarker.

scholarly journals Inhibition of BRD4 inhibits proliferation and promotes apoptosis of psoriatic keratinocytes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaohui Sun ◽  
Pengfei Yang
Keyword(s):  
Mapk Pathway ◽  
Immunohistochemical Analysis ◽  
Severity Index ◽  
Mapk Signaling ◽  
Inflammatory Factors ◽  
Hacat Cells ◽  
Mice Model ◽  
Tnf Α ◽  
Related Proteins

Abstract Background Psoriasis is a common chronic recurrent inflammatory skin disease. The pathogenesis of psoriasis, such as other autoimmune diseases, is still unclear, which brings great difficulties to the treatment. This study aimed to investigate the role of bromine domain protein 4 (BRD4) in affecting the psoriatic keratinocytes. Methods Imiquimod-induced psoriasis mice model and TNF-α or IL-17A induced HaCAT cells, an experimental model in vitro for psoriasis, were constructed. The pathological skin changes at the back of mice were observed by hematoxylin and eosin (H&E) assay and evaluated by psoriasis area and severity index (PASI). KI67 expression and keratinocyte apoptosis at the skin tissues were, respectively, detected by Immunohistochemical analysis and TUNEL assay. The inflammatory factors in mice serum and culture supernatant were determined by ELISA assay. The related proteins expression of proliferation, apoptosis and MAPK pathway were detected by Western blot analysis. Results BRD4 expression was upregulated in injured skin on the back of imiquimod-induced mice and (+)-JQ1 relieved the skin injury by suppressing the inflammation and promoting apoptosis of keratinocytes. Consistently, BRD4 expression was also increased in TNF-α or IL-17A induced HaCAT cells. (+)-JQ1 suppressed the viability and inflammation, and promoted apoptosis of TNF-α or IL-17A induced HaCAT cells. In addition, the MAPK signaling pathway was inhibited by (+)-JQ1 whether in mice or HaCAT cells. Conclusions Inhibition of BRD4 inhibited proliferation and inflammation and promoted apoptosis of psoriatic keratinocytes.

scholarly journals Expression of sirtuins 1, 6, tumor necrosis factor, and interferon-γ in psoriatic patients

2016 ◽  
Vol 29 (4) ◽  
pp. 764-768 ◽  
Author(s):  
H Rasheed ◽  
MHM El-Komy ◽  
RA Hegazy ◽  
HI Gawdat ◽  
AM AlOrbani ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Severity Index ◽  
Interferon Γ ◽  
Novel Therapy ◽  
Lesional Skin ◽  
Tnf Α ◽  
Ifn Γ ◽  
Necrosis Factor ◽  
Control Skin

Sirtuins (SIRT) have been regarded as culprits in the pathogenesis of various diseases. Their exact role has not been explained. This study aimed to assess the expression of SIRT1, SIRT6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in psoriatic patients. Thirty psoriatic patients and 22 controls were enrolled. Clinical examination and Psoriasis Area and Severity Index (PASI) were obtained. Two skin biopsies (lesional, peri-lesional) and one from controls were obtained. Tissue levels of SIRT1, SIRT6, TNF-α, and IFN-γ were measured using ELISA. SIRT1 was significantly lower in lesional skin with gradual increase in perilesional followed by control skin ( P <0.001). SIRT6, TNF-α, and IFN-γ were significantly higher in lesional than perilesional and control skin ( P <0.001). Significant positive correlations were found between SIRT1 and TNF-α, IFN-γ and between SIRT6 and TNF-α in peri-lesional skin. SIRT1 and SIRT6 are potentially involved in the pathogenesis of psoriasis. Modulating their action could offer a novel therapy for such disease.

The time course of inflammatory cytokine secretion in a rat model of postoperative pain does not coincide with the onset of mechanical hyperalgesia

2007 ◽  
Vol 85 (6) ◽  
pp. 613-620 ◽  
Author(s):  
Lisa C. Loram ◽  
Andreas C. Themistocleous ◽  
Linda G. Fick ◽  
Peter R. Kamerman
Keyword(s):  
Postoperative Pain ◽  
Inflammatory Cytokine ◽  
Time Course ◽  
Mechanical Stimulus ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Primary Hyperalgesia ◽  
Factor Α

We characterized the time course of inflammatory cytokine release at the site of injury and in plasma after surgery on the rat tail. Anesthetized Sprague–Dawley rats had a 20 mm long incision made through the skin and fascia of their tails. Control rats were anesthetized, but no incision was made. Blood and tissue samples were taken 2 h and 1, 2, 4, and 8 days after surgery and analysed by ELISA for interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In another group of rats, daily behavioral measurements were made of the rats’ responses to a blunt noxious mechanical stimulus (4 Newtons) applied to their tails. Primary hyperalgesia developed within 2 h of surgery and lasted for 6 days. The tissue concentrations of IL-1β, IL-6, and CINC-1 increased within 24 h of surgery, and TNF-α concentration increased within 48 h of surgery. Thereafter, cytokine concentrations remained elevated for 4 (IL-1β and IL-6) to 8 days (CINC-1, TNF-α) after surgery. Control animals did not develop hyperalgesia and no changes in cytokines concentrations were detected. Thus, in our model of postoperative pain, secretion of inflammatory cytokines IL-1β, IL-6, TNF-α, and CINC-1 was not essential for the initiation of postoperative hyperalgesia.

scholarly journals The Molecular Analysis of rs11614913 Polymorphism from miRNA196a Gene and Its Relationship with TNF-α Gene Expression in Cervical Cancer

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ahmad Hamta ◽  
Fatemeh Hajihassani
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Malignant Tumors ◽  
Control Group ◽  
Tissue Samples ◽  
Altered Expression ◽  
Tnf Α ◽  
Cancer Sample ◽  
Rs11614913 Polymorphism ◽  
Factor Α

Background: Cervical cancer (CC) is one of the most common malignant tumors in women, which has been diagnosed as fourth cancer in females worldwide. In addition to human papillomavirus (HPV), genetic factors, including altered expression of some microRNAs and mutations in tumor necrosis factor α (TNF-α) gene, are involved in this cancer. Objectives: This study aimed to investigate the rs11614913 polymorphism from the miRNA196a gene and its association with the expression of the TNF-α gene in cervical cancer for early diagnosis and treatment. Methods: In this study, 52 samples of pre-cancerous and cancerous lesions, and 50 tissue samples were collected from healthy subjects in an Iranian population. DNA was extracted from the samples, and rs11614913 polymorphism of the miRNA196a gene was investigated by PCR. RNA was extracted from the samples, and the expression of the miRNA196a and TNF-α genes were evaluated. Finally, for data analysis, Epi Info software version 7.1.3.10 and MedCalc Version 19.2.0 were used. Results: The frequency of CC, TC, and TT genotypes from rs11614913 polymorphism of miRNA196a gene was 0.58, 0.34, and 0.08, respectively, but in the healthy group it was 0.36, 0.46, and 0.18, respectively. The results also showed that the expression of miRNA196a and TNF-α genes in the patient group was higher than the control group. Conclusions: Based on the results of this study, a significant correlation was found between CC genotype and rs11614913 polymorphism of miRNA196a gene and TNF-α gene expression in the cervical cancer sample. Therefore, investigating these factors in patients with cervical cancer may be helpful.

scholarly journals The effect of apremilast therapy on skin cytokine levels in patients with psoriasis

2020 ◽  
Vol 9 (3) ◽  
Author(s):  
Alexey A. Kubanov ◽  
Viktoria S. Solomka ◽  
Arfenya E. Karamova ◽  
Dmitry A. Verbenko ◽  
Elena L. Vasileva ◽  
...  
Keyword(s):  
Objective Assessment ◽  
Severity Index ◽  
Cd40 Ligand ◽  
Soluble Cd40 Ligand ◽  
Lesional Skin ◽  
Suspension Array ◽  
Phosphodiesterase 4 ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Skin Samples

Objective — Assessment of phosphodiesterase-4 inhibitor (apremilast) therapy’s influence on skin cytokine levels in patients with moderate-to-severe and severe psoriasis. Material and Methods — An open, uncontrolled study was conducted. 16 patients with plaque psoriasis (13 men, 3 women; mean ± standard deviation (SD) age 35.1±9.7 years, range 21-60) were enrolled. The mean Psoriasis Area and Severity Index (PASI) was 20.7±8.93 (range 10-47). All patients were prescribed apremilast 30 milligrams (mg) per os (PO) Bis In Die (BID). The efficacy of therapy was evaluated by PASI at 14 and 26 weeks of therapy. Lesional skin samples were collected at baseline and weeks 14 and 26. Levels of interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL -33, interferon (INF)-γ, Soluble CD40-ligand (sCD40L), tumor necrosis factor (TNF)-α were measured by microsphere-based suspension array technology (Luminex® xMAP™ system). Results — Levels of cytokines (except IL-4 and IL-33) in lesional skin samples were found to have decreased at week 14 compared with those at baseline. Similar decreases were seen for IL-23, IL-25, IL-31, sCD40L at week 26. In contrast, the levels of other cytokines increased again at week 26, in comparison with baseline. Levels of IL-4 and IL-33 rose throughout the follow-up period. Cytokine levels in lesional skin samples were compared with those of healthy controls both at baseline and during therapy. Conclusion — The results of our study show that administering apremilast therapy to patients with psoriasis can bring the levels of cytokines involved in the IL-23/IL-17 axis in the lesional skin to the level of cytokine in non-lesional skin and to the levels in the skin of healthy individuals.

scholarly journals The effects of chrysin on cypermethrin-induced acute intoxication in rainbow trout (Oncorhynchus mykiss)

2019 ◽  
Vol 27 (2) ◽  
pp. 102-111
Author(s):  
Ozge Cerit ◽  
Feride Koc
Keyword(s):  
Interleukin 1 ◽  
Interleukin 10 ◽  
Control Group ◽  
Interleukin 1 Beta ◽  
Tissue Samples ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Tnf Α ◽  
Factor Α ◽  
Oxidative Effects ◽  
Necrosis Factor

Abstract Cypermethrin (CP) is a toxic insecticide to fishes. Chrysin (CR) is a flavonoid, which can be obtained from plants. The aim of this study was to determine the effects of CR in fishes that had acute CP toxicity. In the study, a total of 60 fishes were used and added to feed and water with CR and CP for 10 days. Blood and tissue samples were collected. The serum enzymes aspartate transaminase (AST) and alanine aminotransferase (ALT), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) levels/activities were determined for liver and kidneys. In this study, when the CP group was compared to the control group, an increase was observed in the levels/activities of AST, ALT, IL-1ß, TNF-α, and IL-6, otherwise, there was a decrease in the IL-10 level in the CP group. Additionally, an increase of MDA levels and a decrease of SOD, GSH-Px, and CAT levels/activities were observed in the CP group. When the CP group was compared to the CR groups, there was a decrease in IL-1β, IL-6, TNF-α, ALT, AST, and MDA levels/activities and there was an increase, depending on the dosage in GSH-Px, SOD, and CAT levels/activities of the CR groups. In conclusion, CR can prevent tissue damage, affecting oxidation via anti-inflammatory and anti-oxidative effects of acute toxicity of fishes exposed to CP.

scholarly journals In VitroEvaluation of a Biomedical-Grade Bilayer Chitosan Porous Skin Regenerating Template as a Potential Dermal Scaffold in Skin Tissue Engineering

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Chin Keong Lim ◽  
Ahmad Sukari Halim ◽  
Ismail Zainol ◽  
Kartini Noorsal
Keyword(s):  
Tissue Engineering ◽  
Skin Irritation ◽  
Dermal Fibroblasts ◽  
Skin Tissue ◽  
Skin Tissue Engineering ◽  
Tnf Α ◽  
Factor Α ◽  
Human Epidermal Keratinocyte ◽  
Necrosis Factor

Chitosan is a copolymer ofN-acetylglucosamine and glucosamine. A bilayer chitosan porous skin regenerating template (CPSRT) has been developed for skin tissue engineering. The pore size of the CPSRT was assessed using a scanning electron microscopy (SEM). Thein vitrocytocompatibility of the CPSRT was tested on primary human epidermal keratinocyte (pHEK) cultures by measuring lactate dehydrogenase (LDH) levels and skin irritation by western blot analysis of the interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) secretions. The ability of the CPSRT to support cell ingrowth was evaluated by seeding primary human dermal fibroblasts (pHDFs) on the scaffold, staining the cells with live/dead stain, and imaging the construct by confocal microscopy (CLSM). The CPSRT with pore sizes ranging from 50 to 150 μm was cytocompatible because it did not provoke the additional production of IL-8 and TNF-α by pHEK cultures. Cultured pHDFs were able to penetrate the CPSRT and had increased in number on day 14. In conclusion, the CPSRT serves as an ideal template for skin tissue engineering.

scholarly journals Psoriasis Features in Patients with Inflammatory Bowel Disease

2019 ◽  
Vol 7 (6) ◽  
pp. 1001-1003
Author(s):  
Maddalena Napolitano ◽  
Anna Testa ◽  
Maria Ferrillo ◽  
Alessia Villani ◽  
Nicola Balato ◽  
...  
Keyword(s):  
Severity Index ◽  
Immunosuppressive Drugs ◽  
Psoriasis Area Severity Index ◽  
Severity Index Score ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
One Year ◽  
Factor Α ◽  
The University

BACKGROUND: Psoriasis and inflammatory bowel diseases (IBD) share common pathways based on immune dysregulation with an important role of tumour necrosis factor-α and Th17 cells, as well as the genetic background. Several studies showed an increased prevalence of psoriasis in IBD patients. However, data regarding psoriasis features in IBD patients are still lacking. AIM: We aimed to conduct an observational study to assess psoriasis clinical features and its severity in a group of patients with IBD. METHODS: Dermatological assessment was performed consecutively in 200 IBD patients (123 with CD and 77 with UC) attending the IBD Care Centre of Gastroenterology at the University of Naples Federico II from 2015 to 2016. RESULTS: A group of 32 from 200 IBD patients (16%) had a familiar history positive for psoriasis, whereas, medical history and dermatologic examination revealed that 18 (9%) IBD patients were affected by psoriasis: 11 out of these 18 subjects (61.2%) had CD, and 7 had UC (38.2%); no significant differences were found between CD and UC groups. Concerning psoriasis severity, the mean psoriasis area severity index score was 3.7. CONCLUSION: This one-year retrospective study showed that psoriasis and IBD both require the use of immunosuppressive drugs so; we can count on a better treatment outcome for both diseases.

Genetic Variation in TNF-α, its Relation with Inflammatory Biomarkers and Susceptibility to Rheumatoid Arthritis

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Level ◽  
Functional Disability ◽  
Serum Levels ◽  
Amplification Refractory Mutation System ◽  
Reactive Protein ◽  
Tnf Α ◽  
Mutation System ◽  
Potential Factor ◽  
Factor Α

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.

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