The influence of antimalarial treatment on IL-1β, IL-6 and TNF-α mRNA expression on UVB-irradiated skin in systemic lupus erythematosus

Author(s):  
A. Wozniacka ◽  
A. Lesiak ◽  
J. Boncela ◽  
K. Smolarczyk ◽  
D.P. McCauliffe ◽  
...  
1998 ◽  
Vol 48 (5) ◽  
pp. 551-556 ◽  
Author(s):  
ALVARADO-DE LA BARRERA ◽  
ALCOCER-VARELA ◽  
RICHAUD-PATIN ◽  
ALARCÓN-SEGOVIA ◽  
LLORENTE

Clinics ◽  
2011 ◽  
Vol 66 (1) ◽  
pp. 77-82 ◽  
Author(s):  
José Ronaldo M Carneiro ◽  
Hellen T Fuzii ◽  
Cristiane Kayser ◽  
Fernando L Alberto ◽  
Fernando A Soares ◽  
...  

Lupus ◽  
2021 ◽  
pp. 096120332110047
Author(s):  
Andrea Latini ◽  
Lucia Novelli ◽  
Fulvia Ceccarelli ◽  
Cristiana Barbati ◽  
Carlo Perricone ◽  
...  

Background Systemic Lupus Erythematosus (SLE) is a complex chronic autoimmune disease characterized by several immunological alterations. T cells have a peculiar role in SLE pathogenesis, moving from the bloodstream to the peripheral tissues, causing organ damage. This process is possible for their increased adherence and migration capacity mediated by adhesion molecules, such as CD44. Ten different variant isoforms of this molecule have been described, and two of them, CD44v3 and CD44v6 have been found to be increased on SLE T cells compared to healthy controls, being proposed as biomarkers of disease and disease activity. The process of alternative splicing of CD44 transcripts is not fully understood. We investigated the mRNA expression of CD44v3 and CD44v6 and also analyzed possible CD44 splicing regulators (ESRP1 molecule and rs9666607 CD44 polymorphism) in a cohort of SLE patients compared to healthy controls. Methods This study involved 18 SLE patients and 18 healthy controls. Total RNA and DNA were extracted by peripheral blood mononuclear cells. The expression study was conducted by quantitative RT-polymerase chain reaction, using SYBR Green protocol. Genotyping of rs9666607 SNP was performed by direct sequencing. Results CD44v6 mRNA expression was higher in SLE patients compared to healthy controls (p = 0.028). CD44v3/v6 mRNA ratio in healthy controls was strongly unbalanced towards isoform v3 compared to SLE patients (p = 0.002) and decreased progressively from healthy controls to the SLE patients in remission and those with active disease (p = 0.015). The expression levels of CD44v3 and CD44v6 mRNA correlated with the disease duration (p = 0.038, Pearson r = 0.493 and p = 0.038, Pearson r = 0.495, respectively). Splicing regulator ESRP1 expression positively correlated with CD44v6 expression in healthy controls (p = 0.02, Pearson r = 0.532) but not in SLE patients. The variant A allele of rs9666607 of CD44 was associated with higher level of global CD44 mRNA (p = 0.04) but not with the variant isoforms. Conclusions In SLE patients, the increase in CD44v6 protein correlates with a higher transcript level of this isoform, confirming an impairment of CD44 splicing in the disease, whose regulatory mechanisms require further investigation.


2010 ◽  
Vol 37 (4) ◽  
pp. 766-775 ◽  
Author(s):  
JIE LI ◽  
HONGFU XIE ◽  
TING WEN ◽  
HONGBO LIU ◽  
WU ZHU ◽  
...  

Objective.To compare the expression of high mobility group box chromosomal protein 1 (HMGB1) and the modulating effects on its downstream cytokines in patients with systemic lupus erythematosus (SLE) and healthy controls.Methods.HMGB1 concentrations in serum from SLE patients and controls were measured by immunoblot analysis. HMGB1 messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMC) was detected by real-time reverse transcription–polymerase chain reaction. Immunofluorescence assay was employed to examine the translocation of HMGB1 in monocytes after endotoxin stimulation. Release of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) by PBMC after rHMGB1 stimulation was also measured.Results.Serum HMGB1 levels and HMGB1 mRNA expressions in PBMC were elevated in SLE patients compared with controls. A positive correlation was demonstrated between HMGB1 concentrations and SLE Disease Activity Index. There was an inverse correlation between HMGB1 levels and C4 and C3 concentrations in SLE patients. HMGB1 concentrations were higher in patients with vasculitis and myositis. Lipopolysaccharide stimulated a temporarily elevated release of HMGB1 in SLE patients compared with controls. The pattern and localization of HMGB1 staining in monocytes were similar in both groups. After stimulation with rHMGB1, TNF-α level decreased but IL-6 level increased in SLE patients compared with controls.Conclusion.Our findings suggest that increased serum levels of HMGB1 in SLE may be associated with lupus disease activity. The altered production of TNF-α and IL-6 in response to rHMGB1 stimulation may participate in the disruption of cytokine homeostasis in SLE.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Amal H. Uzrail ◽  
Areej M. Assaf ◽  
Shtaywy S. Abdalla

Systemic lupus erythematosus (SLE) is characterized by systemic end-organ damage. We investigated the involvement of IRF5, TLR-7, MECP2, STAT4, and TNFSF4 genes and TNF-α, IFN-γ, IL-2, IL-12, IL-6, and IL-10 cytokines in SLE pathogenesis and in organ damage in Jordanian patients. Blood was collected from 51 patients and 50 controls. Expression levels of SLE genes in PBMCs and cytokine levels were determined using RT-PCR and ELISA, respectively. Expression levels of all genes and levels of TNF-α, IL-12, IL-6, and IL-10 were higher in SLE patients than those in controls (p<0.05), whereas IL-2 level was lower. High STAT4 (α), TNFSF4, and IL-10 levels correlated with cardiovascular damage, and high MECP2 (α) and TNF-α correlated with renal damage. Pulmonary and musculoskeletal damages correlated with high levels of TNFSF4. We concluded that STAT4 and TNFSF4 genes with TNF-α and IL-10 cytokines could be used as biomarkers to assess SLE activity and manage treatment.


Folia Medica ◽  
2015 ◽  
Vol 57 (2) ◽  
pp. 89-92 ◽  
Author(s):  
Zornitsa G. Kamenarska ◽  
Maria H. Hristova ◽  
Anton I. Vinkov ◽  
Lyubomir A. Dourmishev

Abstract Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which engages most of the immune cells in its development. Various studies concerning the application of antibodies against TNF-α, BlyS, CD20, CD22, IL-6R and complement factors in treatment of SLE have been recently conducted and in spite of the good results reported by some of them, no definite conclusion on their risk-benefit profile can be drawn. The current review summarizes the results obtained in the field and reveals the perspectives for the development of new and more effective strategies for SLE treatment in combination with other immunomodulating drugs.


2020 ◽  
Vol 39 (9) ◽  
pp. 2611-2617
Author(s):  
Tingting Zhu ◽  
Jiaqi Hong ◽  
Zongwen Shuai ◽  
Shengqian Xu ◽  
Danfeng Qian ◽  
...  

Abstract Objective The IKBKE has been proven to be associated with systemic lupus erythematosus (SLE) in a genome-wide association study (GWAS) conducted by our group. The objective of the recent study is to investigate the contribution of IKBKE functional variants (rs2297550) to SLE. Methods We detected the regulatory effect of rs2297550 on IKBKE expression by expression quantitative trait loci (eQTL) study. Then, we investigated the differences of IKBKE mRNA expression levels in peripheral blood mononuclear cells (PBMCs) between 135 SLE patients and 130 healthy controls using quantitative real-time PCR (qRT-PCR). We further analyzed the association of SLE clinical characteristics with IKBKE mRNA expression and rs2297550 polymorphisms. Results The results of eQTL indicated the genotype “GG” of single-nucleotide polymorphism (SNP) rs2297550 was associated with lower expression levels of IKBKE (P = 0.022) in normal controls. Compared with the healthy control group, the expression levels of IKBKE mRNA in patients with SLE were significantly decreased (P = 2.32 × 10−12). In clinical characteristics, we found that IKBKE mRNA expression levels were associated with vasculitis (P = 0.015) and increased C-reactive protein (CRP) (P = 0.021) in SLE patients. Conclusion In this study, we not only detected that the variant rs2297550 of IKBKE may be closely related to SLE, but also proposed functional hypotheses for the association signals. Key Points• The rs2297550 is located in a region with transcriptional regulatory function and may regulate the expression of IKBKE via these regulatory elements.• The genotype “GG” of SNP rs2297550 was associated with lower expression levels of IKBKE.• The expression of IKBKE mRNA was decreased in SLE patients compared with healthy controls.• IKBKE contributes to the clinical characteristics of SLE.


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