The effect of α1-antitrypsin deficiency combined with increased bacterial loads on chronic obstructive pulmonary disease pharmacotherapy: A prospective, parallel, controlled pilot study

Hennawy, Marwa G.; Elhosseiny, Noha M.; Sultan, Hussein; Abdelfattah, Wael; Akl, Yousry; Sabry, Nirmeen A.; Attia, Ahmed S.

doi:10.1016/j.jare.2016.05.002

Cited by 4 publications

(3 citation statements)

References 42 publications

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“…The AAT levels in serum samples were determined using the Human alpha 1 Antitrypsin ELISA Kit (SERPINA1) (ab189579) (Abcam, Cambridge, United Kingdom), as reported (Hennawy et al, 2016). Diluted sera and antibody cocktails were incubated with AAT antibodies in pre-coated wells.…”

Section: Serum Aat Levels Determinationmentioning

confidence: 99%

SERPINA1 Gene Promoter Is Differentially Methylated in Peripheral Blood Mononuclear Cells of Pregnant Women

Rotondo

Otòn-Gonzalez

Selvatici

et al. 2020

Front. Cell Dev. Biol.

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SERine Protein INhibitor-A1 (SERPINA1) is an inducible blood cell gene coding for alpha1-antitrypsin (AAT), a plasma protease inhibitor whose circulating levels are raised during inflammation, infection and advanced pregnancy. DNA methylation has been suggested to play a role in SERPINA1 gene expression regulation in peripheral blood mononuclear cells (PBMCs). The methylation status of SERPINA1 in PBMCs is unknown. The aim of this study was to evaluate the methylation profile of the SERPINA1 promoter in PBMC. To this purpose PBMCs and serum were collected from healthy subjects (HS) (n = 75), including blood donors (BD) (n = 25), pregnant women at early pregnancy (EP) (n = 25), i.e., within the first trimester, and pregnant women at late pregnancy (LP) (n = 25), i.e., at the third trimester. DNA from PBMCs was treated with sodium bisulfite and PCR amplified for SERPINA1 gene promoter, followed by sequencing analyses. AAT serum levels were determined by ELISA test. SERPINA1 was found hypermethylated in 58.7% of HS. The prevalence of SERPINA1 hypermethylation was significantly higher in BD (68%) and EP (88%) than in LP (20%) (p < 0.01). The median serum AAT concentration was 1.07, 0.63, and 3.15 mg/ml in BD, EP, and LP, respectively (p < 0.05, BD and EP vs LP). This study indicates, for the first time, that SERPINA1 gene promoter is differentially methylated in PBMCs from HS. Likely, modulation of the methylation may be a novel epigenetic regulator mechanism of AAT expression in the PBMC of HS. Therefore, SERPINA1 gene promoter methylation may represent an epigenetic biomarker of PBMCs in healthy subjects.

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Section: Serum Aat Levels Determinationmentioning

confidence: 99%

SERPINA1 Gene Promoter Is Differentially Methylated in Peripheral Blood Mononuclear Cells of Pregnant Women

Rotondo

Otòn-Gonzalez

Selvatici

et al. 2020

Front. Cell Dev. Biol.

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“…An increase in AAT expression may also contribute to activation of signaling events that initiate the production and release of pro-inflammatory cytokines and adhesion molecules, such as lipopolysaccharides, TNF-α, IL-1 and IL-6, which are released by neutrophils, monocytes, macrophages and alveolar macrophages that may in turn activate innate immunity and inflammatory responses ( 13-15 ). A number of studies have suggested that AAT is associated with the development of chronic hepatitis, liver cirrhosis ( 16 ), chronic obstructive pulmonary disease ( 17 ), atherosclerotic diseases ( 18 ), tumors ( 19 ) and autoimmune diseases ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Association between α1‑antitrypsin and acute coronary syndrome

Liu

Huang

et al. 2020

Exp Ther Med

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α1-antitrypsin (AAT) is a protein released as part of the anti-inflammatory response. It regulates the activity of serine proteinases and has a crucial role in the pathogenesis of acute coronary syndrome (ACS). The present study aimed to examine its role in patients with ACS. The plasma samples of 117 patients were collected at the Cardiology Department of the Affiliated Hospital of Youjiang Medical University (Baise, China). These included 46 cases of ACS (who met the diagnostic criteria for ACS and had ≥50% luminal stenosis of any coronary vessel), 35 cases of stable angina (SA; with ≥50% luminal stenosis of any coronary vessel but in a stable condition) and 36 normal healthy controls (subjects with no luminal stenosis in their coronary arteries). Plasma AAT protein concentrations were measured by ELISA and clinical data were collected. The plasma levels of AAT protein in patients with ACS were lower than those in controls and cases of SA (P<0.05), and the levels tended to decrease with the number of coronary artery lesions involved. There were no significant associations of the expression of plasma AAT protein and the number of diseased vessels in patients or the degree of stenosis. There was no correlation between the plasma protein levels of AAT and Gensini scores of patients with ACS. In conclusion, the plasma AAT protein levels in patients with ACS may contribute to the occurrence and development of coronary artery disease.

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“…AAT levels in serum samples were determined using the Human alpha 1 Antitrypsin enzyme‐linked immunosorbent assay (ELISA) Kit ( SERPINA1 ) (product no. ab189579, Abcam), as previously described (10).…”

Section: Methodsmentioning

confidence: 99%

Neutrophil Extracellular Trap–Borne Elastase Prevents Inflammatory Relapse in Intercritical Gout

Liu

Shan

Wang

et al. 2023

Arthritis & Rheumatology

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Objective. Gout flares that occur during urate-lowering therapy (ULT) are typically related to the shrinkage of tophi due to aggregated neutrophil extracellular traps (NETs) that have captured monosodium urate crystals in the tissues. The present study was undertaken to analyze the blocking effect of α 1 -antitrypsin on neutrophil elastase, and it was found that α 1 -antitrypsin induced rapid inflammation in the presence of unstable tophi.Methods. Cell-free DNA levels in serum samples were compared between patients who experienced a varying number of gout flares. We investigated whether cell-free DNA in serum samples and α 1 -antitrypsin could be altered after the initiation of ULT. In mice, an injection of monosodium urate monohydrate (MSU) crystals was used to form a mimic of tophi in the peritoneal cavity, which was then analyzed using immunofluorescence staining. Finally, we investigated the relapse of inflammation by analyzing the levels of α 1 -antitrypsin in 2 kinds of artificial tophi and in tophusbearing mice.Results. Levels of cell-free DNA in serum samples correlated with the number of flares experienced by patients with tophaceous gout. ULT induced an increase in cell-free DNA in the serum of patients with tophi. Increases in levels of α 1 -antitrypsin were seen in patients with tophi who received ULT. Chalk-like tophi removed from the peritoneal cavity of mice after MSU crystals induced inflammation showed abundant coexpression of interleukin-1β (IL-1β) and IL-6-associated NETs. A relapse in inflammation was induced by α 1 -antitrypsin during the spontaneous resolution of MSU crystal-induced peritonitis. We observed that α 1 -antitrypsin blocks cytokine degradation by neutrophil elastase during the resolution phase of tophi.Conclusion. ULT causes shrinkage of the tophi reflected by an increase in the levels of cell-free DNA in serum. In the resolution phase of tophi in mice, NET-associated neutrophil elastase degrades proinflammatory cytokines and, thus, ameliorates inflammation.

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The effect of α1-antitrypsin deficiency combined with increased bacterial loads on chronic obstructive pulmonary disease pharmacotherapy: A prospective, parallel, controlled pilot study

Abstract: Graphical abstract

Cited by 4 publications

References 42 publications

SERPINA1 Gene Promoter Is Differentially Methylated in Peripheral Blood Mononuclear Cells of Pregnant Women

SERPINA1 Gene Promoter Is Differentially Methylated in Peripheral Blood Mononuclear Cells of Pregnant Women

Association between α1‑antitrypsin and acute coronary syndrome

Neutrophil Extracellular Trap–Borne Elastase Prevents Inflammatory Relapse in Intercritical Gout

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The effect of α1-antitrypsin deficiency combined with increased bacterial loads on chronic obstructive pulmonary disease pharmacotherapy: A prospective, parallel, controlled pilot study

Abstract: Graphical abstract

Cited by 4 publications

References 42 publications

SERPINA1 Gene Promoter Is Differentially Methylated in Peripheral Blood Mononuclear Cells of Pregnant Women

SERPINA1 Gene Promoter Is Differentially Methylated in Peripheral Blood Mononuclear Cells of Pregnant Women

Association between &alpha;1‑antitrypsin and acute coronary syndrome

Neutrophil Extracellular Trap–Borne Elastase Prevents Inflammatory Relapse in Intercritical Gout

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Association between α1‑antitrypsin and acute coronary syndrome