Gelsolin decreases actin toxicity and inflammation in murine multiple sclerosis

Li-Chun, Hsieh Kevin; Schob, Stefan; Zeller, Matthias W.G.; Pulli, Benjamin; Ali, Muhammad; Wang, Cuihua; Chiou, Terry Ting-Yu; Tsang, Yuk‐Ming; Lee, Po‐Shun; Stossel, Thomas P.; Chen, John W.

doi:10.1016/j.jneuroim.2015.08.006

Cited by 25 publications

(7 citation statements)

References 36 publications

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“…In addition to its role as a novel biomarker, gelsolin has therapeutic potential. In mouse models of sepsis and multiple sclerosis where gelsolin levels were depleted, administration of recombinant gelsolin proteins improved survival and brain inflammation 31 , 40 . In a recent preliminary clinical trial, the safety of rhu-pGSN was established in humans 38 .…”

Section: Discussionmentioning

confidence: 99%

Gelsolin and Progression of Aortic Arch Calcification in Chronic Hemodialysis Patients

Chiou¹,

Liao²,

Kao³

et al. 2016

Int. J. Med. Sci.

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Background:Vascular calcification (VC) is a key process associated with cardiovascular mortality in dialysis patients. Gelsolin is an actin-binding protein that can modulate inflammation, correlated inversely with hemodialysis (HD) mortality and involved in bone calcification homeostasis. In this report, we aim to characterize progression in aortic arch calcification (AAC) and investigate its association with gelsolin.Methods: 184 HD patients were enrolled and their annual posterior-anterior chest X-ray films (CXR) in 2009 and 2013 were examined. The severity of AAC was classified as grade 0 to 3. Blood levels of gelsolin were measured by ELISA kits. Biographic and biochemical data at baseline were analyzed with status of AAC at baseline and changes after 4 years.Results: At baseline, 60% of the patients had detectable AAC on CXR. After 4 years, 77% had AAC. Patients with grade 1 and 2 AAC had increased risk of progression (Odds ratio [OR] 2~3, P=0.001) compared to those with grade 0 at baseline. Compared to those with no AAC, patients with AAC progression had older age, lower gelsolin, higher waist circumference and prevalence of vascular disease. Regression analysis confirmed baseline gelsolin (odds ratio 0.845, 95% confidence interval [0.734-0.974]) and waist circumference as the independent factors associated with AAC progression. Gelsolin is positively correlated with serum albumin and negatively with tumor necrosis factor-alpha.Conclusion: Our study demonstrated that HD patients with grades 1 or 2 baseline AAC are at increased risk of further progression compared to those with grade 0. We also found lower blood levels of gelsolin associated with progressive AAC. Further investigation into the mechanistic roles of gelsolin in vascular calcification may provide new understanding of this key process.

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Section: Discussionmentioning

confidence: 99%

Gelsolin and Progression of Aortic Arch Calcification in Chronic Hemodialysis Patients

Chiou¹,

Liao²,

Kao³

et al. 2016

Int. J. Med. Sci.

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“…Interestingly, recombinant human pGSN exerts its therapeutic effect not only during EAE induction but also on days 8 and 10, during development of neuroinflammation and onset of early symptoms. In addition, delayed treatment with rhp-GSN produced faster and more complete resolution of the clinical symptoms, which is likely determined by higher bioavailability of this protein [ 35 ].…”

Section: Alterations In Plasma Gelsolin Concentrations In Differenmentioning

confidence: 99%

“…Research performed using mouse models of pain and acute inflammation suggested analgesic and anti-inflammatory properties of GSN [ 34 ]. Further studies using gelsolin-null mice revealed a role for gelsolin in cancer development, pathogenesis of diabetes, neurodegenerative diseases, and involvement in osteoblast metabolism [ 35 , 36 , 37 ]. In order to accurately evaluate the role of plasma gelsolin in these processes, it is crucial to develop animal models characterized by the knockout of extracellular gelsolin only, not of total GSN.…”

Section: Introductionmentioning

confidence: 99%

Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

Piktel

Levental

Durnaś

et al. 2018

IJMS

113

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Gelsolin, an actin-depolymerizing protein expressed both in extracellular fluids and in the cytoplasm of a majority of human cells, has been recently implicated in a variety of both physiological and pathological processes. Its extracellular isoform, called plasma gelsolin (pGSN), is present in blood, cerebrospinal fluid, milk, urine, and other extracellular fluids. This isoform has been recognized as a potential biomarker of inflammatory-associated medical conditions, allowing for the prediction of illness severity, recovery, efficacy of treatment, and clinical outcome. A compelling number of animal studies also demonstrate a broad spectrum of beneficial effects mediated by gelsolin, suggesting therapeutic utility for extracellular recombinant gelsolin. In the review, we summarize the current data related to the potential of pGSN as an inflammatory predictor and therapeutic target, discuss gelsolin-mediated mechanisms of action, and highlight recent progress in the clinical use of pGSN.

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“…Plasma gelsolin (pGSN) is a multifunctional, actin-binding protein involved in a number of physiological and pathological processes including, but not limited to, the removal of actin filaments from the bloodstream leaked from dead cells as the result of tissue injury [1,2]. Recently, pGSN was recognized as a key factor modulating host immune responses due to the preferential binding of microbial-derived endotoxins, resulting in prevention of toll-like receptor (TLR) activation [3,4].…”

Section: Introductionmentioning

confidence: 99%

Recombinant Human Plasma Gelsolin Stimulates Phagocytosis while Diminishing Excessive Inflammatory Responses in Mice with Pseudomonas aeruginosa Sepsis

Piktel

Wnorowska

Cieśluk

et al. 2020

IJMS

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Plasma gelsolin (pGSN) is a highly conserved abundant circulating protein, characterized by diverse immunomodulatory activities including macrophage activation and the ability to neutralize pro-inflammatory molecules produced by the host and pathogen. Using a murine model of Gram-negative sepsis initiated by the peritoneal instillation of Pseudomonas aeruginosa Xen 5, we observed a decrease in the tissue uptake of IRDye®800CW 2-deoxyglucose, an indicator of inflammation, and a decrease in bacterial growth from ascitic fluid in mice treated with intravenous recombinant human plasma gelsolin (pGSN) compared to the control vehicle. Pretreatment of the murine macrophage line RAW264.7 with pGSN, followed by addition of Pseudomonas aeruginosa Xen 5, resulted in a dose-dependent increase in the proportion of macrophages with internalized bacteria. This increased uptake was less pronounced when cells were pretreated with pGSN and then centrifuged to remove unbound pGSN before addition of bacteria to macrophages. These observations suggest that recombinant plasma gelsolin can modulate the inflammatory response while at the same time augmenting host antibacterial activity.

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Gelsolin decreases actin toxicity and inflammation in murine multiple sclerosis

Cited by 25 publications

References 36 publications

Gelsolin and Progression of Aortic Arch Calcification in Chronic Hemodialysis Patients

Gelsolin and Progression of Aortic Arch Calcification in Chronic Hemodialysis Patients

Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

Recombinant Human Plasma Gelsolin Stimulates Phagocytosis while Diminishing Excessive Inflammatory Responses in Mice with Pseudomonas aeruginosa Sepsis

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