Elevated levels of soluble fractalkine and increased expression of CX3CR1 in neuropsychiatric systemic lupus erythematosus

Guo, Ling; Lu, Xinya; Wang, Yuan; Bao, Chunde; Chen, Shun‐le

doi:10.3892/etm.2017.4862

Cited by 12 publications

(8 citation statements)

References 35 publications

(40 reference statements)

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“…Changes in CX3CL1 concentration have been found in other diseases that course with inflammation. For example, soluble CX3CL1 levels are increased in plasma and CSF of patients with lupus erythematosus ( Guo et al, 2017 ). In addition, plasma CX3CL1 levels are augmented in individuals with type-2 diabetes ( Sindhu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Decreased CX3CL1 Levels in the Cerebrospinal Fluid of Patients With Alzheimer’s Disease

et al. 2018

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Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the presence of neurofibrillary tangles, constituted by tau protein, and plaques formed by amyloid-beta protein. The disease courses with high neural damage, which leads to memory loss and death. Here we analyzed the presence of CX3CL1, a chemokine expressed by neurons, in cerebrospinal fluid (CSF) samples from control subjects and patients with mild cognitive impairment and AD dementia. CX3CL1 was decreased in the CSF of AD dementia patients compared to control subjects. However, there was not difference in plasma samples from the same subjects.

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Section: Discussionmentioning

confidence: 99%

Decreased CX3CL1 Levels in the Cerebrospinal Fluid of Patients With Alzheimer’s Disease

et al. 2018

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“…FKN levels are significantly higher in cerebrospinal fluid samples from patients with SLE-associated involvement of the central nervous system (termed neuropsychiatric SLE) than from healthy subjects, and the FKN levels correlate with treatment effects. 76 Similarly, both cerebrospinal fluid and serum levels of FKN are significantly higher in patients with diffuse neuropsychiatric SLE than in patients with other SLE subtypes or in healthy subjects. 76 These results further support a role for FKN in the pathogenesis of SLE, at least neuropsychiatric SLE, and suggest that FKN could serve as a therapeutic target and/or a biomarker for SLE disease activity.…”

Section: Fkn–cx3cr1 Axis Involvement In the Pathogenesis Of Rheumaticmentioning

confidence: 97%

“… 76 Similarly, both cerebrospinal fluid and serum levels of FKN are significantly higher in patients with diffuse neuropsychiatric SLE than in patients with other SLE subtypes or in healthy subjects. 76 These results further support a role for FKN in the pathogenesis of SLE, at least neuropsychiatric SLE, and suggest that FKN could serve as a therapeutic target and/or a biomarker for SLE disease activity.…”

Section: Fkn–cx3cr1 Axis Involvement In the Pathogenesis Of Rheumaticmentioning

confidence: 97%

<p>Emerging Role of Fractalkine in the Treatment of Rheumatic Diseases</p>

Tanaka¹,

Hoshino-Negishi²,

Kuboi³

et al. 2020

ITT

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Rheumatoid arthritis (RA) is an autoimmune disorder that affects joints and is characterized by synovial hyperplasia and bone erosion associated with neovascularization and infiltration of proinflammatory cells. The introduction of biological disease-modifying anti-rheumatic drugs has dramatically changed the treatment of RA over the last 20 years. However, fewer than 50% of RA patients enter remission, and 10–15% are treatment refractory. There is currently no cure for RA. Fractalkine (FKN, also known as CX3CL1) is a cell membrane-bound chemokine that can be induced on activated vascular endothelial cells. FKN has dual functions as a cell adhesion molecule and a chemoattractant. FKN binds specifically to the chemokine receptor CX3CR1, which is selectively expressed on subsets of immune cells such as patrolling monocytes and killer lymphocytes. The FKN–CX3CR1 axis is thought to play important roles in the initiation of the inflammatory cascade and can contribute to exacerbation of tissue injury in inflammatory diseases. Accordingly, studies in animal models have shown that inhibition of the FKN–CX3CR1 axis not only improves rheumatic diseases but also reduces associated complications, such as pulmonary fibrosis and cardiovascular disease. Recently, a humanized anti-FKN monoclonal antibody, E6011, showed promising efficacy with a dose-dependent clinical response and favorable safety profile in a Phase 2 clinical trial in patients with RA (NCT02960438). Taken together, the preclinical and clinical results suggest that E6011 may represent a new therapeutic approach for rheumatic diseases by suppressing a major contributor to inflammation and mitigating concomitant cardiovascular and fibrotic diseases. In this review, we describe the role of the FKN–CX3CR1 axis in rheumatic diseases and the therapeutic potential of anti-FKN monoclonal antibodies to fulfill unmet clinical needs.

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“…FKN represents one of the factors associated with tissue damage and the accumulation of immune cells into the damaged area (30). Accumulated evidence has suggested that FKN plays a significant role in the disease progression of LN (31). Moreover, we have previously demonstrated that FKN expression was increased in LN model mice and HK-2 cells that were stimulated with lipopolysaccharide, whereas the protein expression of FKN was decreased after methylprednisolone therapy (32).…”

Section: Introductionmentioning

confidence: 99%

FKN Facilitates HK-2 Cell EMT and Tubulointerstitial Lesions via the Wnt/β-Catenin Pathway in a Murine Model of Lupus Nephritis

Senouthai

Wang

et al. 2019

Front. Immunol.

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Fractalkine (FKN), also known as chemokine (C-X3-C motif) ligand 1, constitutes an intriguing chemokine with a documented role in the development of numerous inflammatory diseases including autoimmune disease. Specifically, it has been reported that FKN is involved in the disease progression of lupus nephritis (LN). The epithelial-mesenchymal transition (EMT) plays a significant role in the formation of tubulointerstitial lesions (TIL), which are increasingly recognized as a hallmark of tissue fibrogenesis after injury. However, the correlation between FKN and EMT or TIL in LN has not been determined. To investigate the potential role of FKN in EMT and TIL, MRL lymphoproliferation (MRL/lpr) strain mice were treated with an anti-FKN antibody, recombinant-FKN chemokine domain, or isotype antibody. Our results revealed that treatment with the anti-FKN antibody improved EMT, TIL, and renal function in MRL/lpr mice, along with inhibiting activation of the Wnt/β-catenin signaling pathway. In contrast, administration of the recombinant-FKN chemokine domain had the opposite effect. Furthermore, to further explore the roles of FKN in EMT, we assessed the levels of EMT markers in FKN-depleted or overexpressing human proximal tubule epithelial HK-2 cells. Our results provide the first evidence that the E-cadherin level was upregulated, whereas α-SMA and vimentin expression was downregulated in FKN-depleted HK-2 cells. In contrast, overexpression of FKN in HK-2 cells enhanced EMT. In addition, inhibition of the Wnt/β-catenin pathway by XAV939 negated the effect of FKN overexpression, whereas activation of the Wnt/β-catenin pathway by Ang II impaired the effect of the FKN knockout on EMT in HK-2 cells. Together, our data indicate that FKN plays essential roles in the EMT progression and development of TIL in MRL/lpr mice, most likely through activation of the Wnt/β-catenin signaling pathway.

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Elevated levels of soluble fractalkine and increased expression of CX3CR1 in neuropsychiatric systemic lupus erythematosus

Cited by 12 publications

References 35 publications

Decreased CX3CL1 Levels in the Cerebrospinal Fluid of Patients With Alzheimer’s Disease

Decreased CX3CL1 Levels in the Cerebrospinal Fluid of Patients With Alzheimer’s Disease

<p>Emerging Role of Fractalkine in the Treatment of Rheumatic Diseases</p>

FKN Facilitates HK-2 Cell EMT and Tubulointerstitial Lesions via the Wnt/β-Catenin Pathway in a Murine Model of Lupus Nephritis

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