TNF-α and IL-1 Sequentially Induce Endothelial ICAM-1 and VCAM-1 Expression in MRL/<i>lpr</i>Lupus-Prone Mice

McHale, Julie F.; Harari, Olivier; Marshall, Diane; Haskard, Dorian O.

doi:10.4049/jimmunol.163.7.3993

Cited by 94 publications

(1 citation statement)

References 55 publications

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“…VCAM-1 expression in an animal model has been shown to increase in lupus nephritis (11). It seems that VCAM-1 can signal the progression of nephritis and potentially replace the invasive methods to screen lupus nephritis.…”

Section: Objectivesmentioning

confidence: 99%

The relationship between serum VCAM-1 level and lupus nephritis in patients with systemic lupus erythematosus

Musavi,

Mirfeizi,

Mehrad-Majd

et al. 2020

J Nephropathol

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Introduction: Nephritis is a frequent inflammatory autoimmune complication in systemic lupus erythematosus (SLE). Detecting the nephritis state of SLE patients using non-invasive biomarkers seems to be necessary. Objectives: This study aimed to evaluate role of vascular cell adhesion molecule-1 (VCAM-1) as a noninvasive method in the assessment of lupus nephritis. Patients and Methods: This study was conducted at Imam Reza hospital in Mashhad, Iran, during 2017-2018. A total of 114 SLE patients diagnosed based on the lupus diagnosis criteria including the clinical and paraclinical symptoms that were referred to the rheumatology or nephrology clinics and were enrolled in the study. After obtaining informed consent, a blood sample was taken to determine serum VCAM-1 levels. All patients were evaluated for glomerular hematuria and proteinuria in addition to testing for serum C3, and C4, anti-nuclear antibody (ANA) and anti-ds DNA levels. The serum urea and creatinine levels as well as 24-hour urine protein were measured. Finally, the patients were designed into two groups of SLE with and without nephritis. A renal biopsy was performed in lupus patients with nephritis to determine the class of the disease. The association between serum levels of VCAM-1 and activity of SLE disease [systemic lupus erythematosus disease activity index (SLEDAI)], anti-dsDNA serum level, glomerular hematuria, proteinuria, and lupus nephritis class were evaluated. Results: According to statistical analysis there was no significant relationship between SLEDAI and VCAM-1 levels was detected (P>0.05). Additionally, no significant relationship between VCAM-1 levels and lupus nephritis classes was detected (P>0.05); however the serum VCAM-1 levels were significantly lower in patients with hematuria (P= 0.021). Conclusion: There is no correlation between serum VCAM-1 levels and classes of lupus nephritis. Our data however requires further investigation on its clinical implications.

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Section: Objectivesmentioning

confidence: 99%

The relationship between serum VCAM-1 level and lupus nephritis in patients with systemic lupus erythematosus

Musavi,

Mirfeizi,

Mehrad-Majd

et al. 2020

J Nephropathol

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Sided Stimulation of Endothelial Cells Modulates Neutrophil Trafficking in an In Vitro Sepsis Model

Ahmad,

Linares,

Pietropaoli

et al. 2024

Adv Healthcare Materials

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Sepsis pathophysiology involves complex interactions between vascular endothelium and circulating immune cells. Importantly, while the role of dysregulated polymorphonuclear leukocyte (PMN) transmigration in septic mediated tissue damage is well documented, strategies to mitigate aberrant transmigration across endothelium have yet to yield viable therapeutics. Much of this can be attributed to the usage of animal models in preclinical trials that lack translational relevance. Recently, however, microphysiological systems (MPS) have emerged as novel in vitro mimetics that facilitate the development of human models of disease. With this advancement, we can now directly probe aspects of endothelial physiology that are difficult to assess with other models. Here, we study the role of endothelial cell (EC) apicobasal polarity and how sided presentation of inflammatory cytokines modulates subsequent leukocyte trafficking response by utilizing the µSiM‐MVM (microphysiological system enabled by a silicon membrane – microvascular mimetic). The apicobasal polarity of ECs with respect to inflammation and leukocyte trafficking is a scarcely studied phenomenon that may be critical to understand the dynamic interplay between ECs and PMNs in sepsis and other causes of systemic inflammation. Here we stimulated ECs either apically or basally with a cytokine cocktail to model a septic‐like challenge before introducing healthy donor PMNs into the device. At low concentrations we found that a tissue sided (basally oriented) stimulation generated a stronger PMN transmigratory response versus apical stimulation. Importantly, healthy PMNs were unable to migrate towards a bacterial peptide chemoattractant when ECs were apically stimulated at low doses. This mimics the impaired ability of PMNs to identify a source of infection seen in sepsis, but identifies an EC role in the impairment for the first time, to our knowledge. Only by escalating the apical inflammatory stimulus by a factor of five were we able to overcome the EC barrier and solicit high PMN transmigration levels from the blood to the tissue side of the chip. These results, using the unique capabilities of the µSiM‐MVM, demonstrate that EC apicobasal polarity modulates differential PMN transmigratory behavior in a way that provides insight into the mechanisms underlying sepsis.This article is protected by copyright. All rights reserved

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Interferon regulatory factor 5 is critical for the development of lupus in MRL/lpr mice

Tada¹,

Kondo²,

Aoki³

et al. 2011

Arthritis & Rheumatism

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Objective. Interferon regulatory factor 5 (IRF-5) is a transcription factor that mediates intracellular signals activated by engagement of Toll-like receptors (TLRs). IRF5 polymorphisms are associated with an increased or decreased risk of systemic lupus erythematosus (SLE) in various human populations, but the precise role of IRF5 in SLE development is not fully understood. This study was undertaken to examine the role of IRF5 in the development of murine lupus.Methods. We crossed gene-targeted IRF5-deficient (IRF5 ؊/؊ ) mice with MRL/MpJ-lpr/lpr (MRL/ lpr) mice and examined the progeny for survival, glomerulonephritis, autoantibody levels, immune system cell populations, and dendritic cell function.Results. IRF5 ؊/؊ MRL/lpr mice survived longer than control IRF5 ؉/؉ MRL/lpr mice and displayed only very mild glomerulonephritis. Autoantibodies to SLErelated nuclear antigens were lower in IRF5 ؊/؊ MRL/lpr mouse serum, and numbers of activated CD4؉ T cells were reduced in the spleen. Splenic DCs from IRF5 ؊/؊ MRL/lpr mice produced lower levels of inflammatory cytokines when treated in vitro with TLR-7 or TLR-9 ligands or immune complexes. Interferon-␣ production in response to CpG was also decreased. Conclusion.Our results show that IRF5 is a crucial driver of lupus development in mice, and indicate that IRF5 may be an attractive new target for therapeutic intervention to control disease in SLE patients.

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TNF-α and IL-1 Sequentially Induce Endothelial ICAM-1 and VCAM-1 Expression in MRL/lprLupus-Prone Mice

Cited by 94 publications

References 55 publications

The relationship between serum VCAM-1 level and lupus nephritis in patients with systemic lupus erythematosus

The relationship between serum VCAM-1 level and lupus nephritis in patients with systemic lupus erythematosus

Sided Stimulation of Endothelial Cells Modulates Neutrophil Trafficking in an In Vitro Sepsis Model

Interferon regulatory factor 5 is critical for the development of lupus in MRL/lpr mice

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