Alpha-1 anti-trypsin and CD30 expression occur in parallel in activated T cells

Bashir, Muhammed Salman; Jones, David B.; Wright, Dennis H.

doi:10.1111/j.1365-2249.1992.tb06484.x

Cited by 10 publications

(2 citation statements)

References 29 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[18][19][20][21] Although α1-AT in the blood is mainly produced by the liver, a large number of studies have found that many extrahepatic tissues, including intestinal epithelial cells, alveolar epithelial cells, pancreatic microvascular endothelial cells, monocytes, T lymphocytes, and articular cartilage, can also secrete α1-AT. [22][23][24][25][26] In addition, it has been demonstrated that renal tubular epithelial cells can express α1-AT at both the protein and mRNA levels, and the expression can be upregulated by LPS. 27 Therefore, we hypothesized that α1-AT might also be involved in the inflammatory processes involved in the progression of DKD.…”

Section: Introductionmentioning

confidence: 99%

<p>Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria</p>

Ning¹,

Xiang²,

Xiong³

et al. 2020

DMSO

View full text Add to dashboard Cite

Purpose: Diabetic kidney disease (DKD), which is related to inflammation and immune response, is the primary vascular complication of diabetes mellitus and also the leading etiology of end-stage renal disease. Urinary extracellular vesicles (UEVs) are an attractive source for biomarker detection as they involve molecular constituents derived from their parental sections of the nephron. In this study, we aimed to search for a potential biomarker in UEVs for the early diagnosis and prediction of DKD, especially before the emergence of microalbuminuria. Patients and Methods: UEVs were isolated from the urine of healthy subjects, prediabetic, and diabetic patients with varying degrees of kidney damage by ultracentrifugation, and the extracted UEVs were used to measure alpha1-antitrypsin (α1-AT) by Western blot. To explore the function of α1-AT in the inflammatory process leading to DKD, we silenced the expression of α1-AT in renal tubular epithelial cells using cell transfection techniques to assess the differential expression of the inflammatory factors such as MCP-1 and TNF-α using qRT-PCR. Results: There was no expression of α1-AT in the UEVs of either healthy or pre-diabetic subjects. Its expression was significantly increased in the UEVs of diabetic patients with normoalbuminuria (prior to microalbuminuria), which was more sensitive and more stable than other renal indexes to predict DKD. Additionally, the expression of α1-AT in UEVs was gradually upregulated with the aggravation of DKD and the decline of renal function. In vitro, the mRNA expression of MCP-1 and TNF-α was significantly decreased when the generation of α1-AT in tubular epithelial cells was inhibited under high glucose stimulation. Conclusion: Our results suggest that α1-AT derived from UEVs, especially in diabetic patients with normoalbuminuria, might serve as a potential noninvasive biomarker for diagnosis of DKD early in the development of the disease and may predict the future decline of renal function.

show abstract

Section: Introductionmentioning

confidence: 99%

<p>Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria</p>

Ning¹,

Xiang²,

Xiong³

et al. 2020

DMSO

View full text Add to dashboard Cite

show abstract

“…It may also exert an effect on autophagy, thereby affecting endoplasmic reticulum function 30. At the cellular level, peripheral blood T lymphocytes stimulated with a mitogen display granular cytoplasmic expression of AAT 31. AAT reduces a detrimental tumor necrosis factor alpha-dependent effect on lymph nodes in adipose and pancreatic tissues 32.…”

Section: Discussionmentioning

confidence: 99%

Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury

Shabat

Ya’acov

Ilan

2018

Journal of Clinical and Translational Hepatology

View full text Add to dashboard Cite

Background and Aims: The serine proteinase inhibitor alpha-1 anti-trypsin (AAT) protects the body against protease activity. Several functions of AAT beyond those attributed to its anti-protease activity have been described, among them immunomodulatory and anti-inflammatory properties. The present study aimed to determine the efficacy of AAT for the treatment of immune-mediated liver injury using the models of concanavalin A-induced immune-mediated hepatitis and acetaminophen -induced liver damage.Methods: AAT was administered to mice subjected to concanavalin A-induced immune-mediated hepatitis or 2 h after acetaminophen-induced liver damage. Mice were followed for changes in serum levels of liver enzymes, liver histology, and for interferon gamma serum levels.Results: Treatment with AAT alleviated concanavalin A-induced immune-mediated liver damage, as demonstrated by a reduction in the serum levels of liver enzymes and interferon gamma, and an improved lymphocyte infiltration into the liver on liver biopsies. Moreover, treatment with AAT was associated with alleviation of the acetaminophen-induced liver injury.Conclusions: AAT exerts an hepatoprotective effect on immune-mediated and drug-induced liver damage. The data support its potential use in patients with immune-associated liver disorders.

show abstract

Proteomic analysis of alpha‐1‐antitrypsin in immunoglobulin A nephropathy

Kwak

Wang

Heo

et al. 2007

Proteomics Clinical Apps

View full text Add to dashboard Cite

Immunoglobulin A nephropathy (IgAN) is recognized as the most common form of primary glomerulonephritis worldwide. It is characterized by mesangial cell proliferation with mesangial IgA deposition in the glomeruli, and is usually associated with secondary tubulointerstitial injury. Although significant progress has been made in the clarification of the pathogenesis of IgAN, the exact pathogenetic mechanism remains unclear. To find out the candidate proteins that play an important role in IgAN, renal cortex tissues and urine from IgAN patients were studied. The 2-DE was performed on renal tissues of IgAN and normal controls. A series of spots identified as alpha-1-antitrypsin (AAT) by mass spectrometry, were found to be significantly increased in patients with IgAN. Up-regulation of AAT variants was validated in renal cortex tissues of IgAN using Western blot and 2-DE immunoblot. Lower isoforms (˜48 kDa) and fragments (˜33 kDa), suspected as cleavage forms by proteinase attack, were especially increased in IgAN compared to normal controls. In addition, AAT proteins modified by tyrosine nitration (approximately 57 and 48 kDa), which reflects excessive oxidative stress, were increased in IgAN tissue. Additionally in the urine of IgAN, increase of AAT variants and fragments was detected by 2-DE immunoblot as well as Western blot. Immunohistochemical staining of IgAN kidney tissue revealed that the increase of AAT appeared to be derived from hypertrophic proximal tubules. The AAT staining in the glomerulus was not clear in IgAN. In addition, immunodepletion-zymography showed a positive correlation between AAT and 80-110-kDa proteinases in IgAN tissue. Further studies regarding the functional roles of AAT and the proteinases will allow better understanding of the pathogenesis of IgAN.

show abstract

Alpha-1 anti-trypsin and CD30 expression occur in parallel in activated T cells

Cited by 10 publications

References 29 publications

<p>Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria</p>

<p>Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria</p>

Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury

Proteomic analysis of alpha‐1‐antitrypsin in immunoglobulin A nephropathy

Contact Info

Product

Resources

About