Early Expression Profile of Inflammatory Markers and Kidney Allograft Status

McDaniel, D. Olga; Rigney, Debbie; McDaniel, Kori; Windham, W. Jordan; Redmond, Paul; Williams, Barbara; Zhou, Xinchun; Hawxby, Alan; Butt, Fauzia

doi:10.1016/j.transproceed.2012.08.027

Cited by 15 publications

(7 citation statements)

References 10 publications

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“…We also established AIF-1 variant mRNA expression correlations between PBMCs and SMs in patients with RA and OA, but no statistical differences were observed. This observation did not agree with data from allograft transplantation studies, where AIF-1 expression in PBMCs was positively correlated with the prediction of allograft status or allograft rejection and was proposed as a biomarker for the detection of early allograft rejection [26][27][28].…”

Section: Discussioncontrasting

confidence: 76%

Over-Expression of Allograft Inflammatory Factor-1 (AIF-1) in Patients with Rheumatoid Arthritis

Piotrowska

Słuczanowska-Głąbowska

Kurzawski

et al. 2020

Biomolecules

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Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein that is encoded by the AIF1 gene. The main functions of AIF-1 are the activation of macrophages and enhancing the production of pro-inflammatory cytokines. To date, three different AIF-1 isoforms have been identified. In this study, we examined the expression of AIF-1 isoforms on the level of mRNA, and we compared the percentage of AIF-1-positive white blood cells (WBCs) in blood and AIF-1/CD68 cells in the synovial membranes in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). We examined 15 patients with RA and 15 patients with OA who had previously undergone knee arthroplasty. Peripheral blood and synovial membranes (SMs) were collected from these patients during knee arthroplasty. We identified three AIF-1 mRNA expression variants in peripheral mononuclear cells (PBMCs) and SMs from patients in both groups. Spearman’s rank correlation coefficient tests showed strong, positive, and significant correlations between the three AIF-1 mRNA expression variants in PBMCs and/or SMs in patients with RA and OA. There were no statistically significant correlations for any of the AIF-1 mRNA expression variants between PBMCs and SMs in patients with RA and OA. We observed a statistically significant increased percentage of AIF-1-positive cells in patients with RA in comparison to patients with OA. The percentage of AIF-1-positive cells in the blood of patients with RA and OA was 1.35 ± 0.81% and 0.71 ± 0.25% (p < 0.01), respectively, whereas the percentage of AIF-1/CD68-positive WBC cells in the SMs was 24.05 ± 7.17% and 4.78 ± 1.52% (p < 0.001), respectively. In conclusion, three AIF-1 mRNA expression variants occurred in PBMCs and SM cells in patients with RA and OA. The AIF-1 mRNA expression levels of the variants correlated with each other in PBMCs and SM cells, but there were no statistically significant correlations for AIF-1 mRNA expression variants between PBMCs and SM cells in patients with RA and OA. Both in the blood and SMs, we observed an increased percentage of AIF-1-positive cells in patients with RA in comparison to patients with OA. The above results suggested that AIF-1 was the cytokine involved in the pathogenesis of RA. The precise knowledge of the role of AIF-1 in RA pathogenesis and the development of inflammatory response requires further investigations.

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Section: Discussioncontrasting

confidence: 76%

Over-Expression of Allograft Inflammatory Factor-1 (AIF-1) in Patients with Rheumatoid Arthritis

Piotrowska

Słuczanowska-Głąbowska

Kurzawski

et al. 2020

Biomolecules

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“…A previous study reported that AIF-1-activated macrophages were increased in the infiltrate of clinical rejection biopsies and were associated with clinical rejection episodes, which was the first report on AIF-1 expression in kidney tissue ( 47 ). Subsequent studies have demonstrated that AIF-1 involved in the inflammatory signaling network regulated the innate immune responses ( 48 ), while the genetic variant TT/CT of the AIF-1 gene was associated with a lower risk of renal rejection ( 49 ). Previous studies also indicated that AIF-1 expressed in podocytes and infiltrating inflammatory cells of kidney tissues ( 42 ) was associated with inflammatory reaction, immune regulation and allograft rejection ( 48 , 50 ).…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent studies have demonstrated that AIF-1 involved in the inflammatory signaling network regulated the innate immune responses ( 48 ), while the genetic variant TT/CT of the AIF-1 gene was associated with a lower risk of renal rejection ( 49 ). Previous studies also indicated that AIF-1 expressed in podocytes and infiltrating inflammatory cells of kidney tissues ( 42 ) was associated with inflammatory reaction, immune regulation and allograft rejection ( 48 , 50 ). The results of the present study revealed that AIF-1 expression and infiltration of macrophages occurred in a progressive renal fibrosis model.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of allograft inflammatory factor‑1 expression and secretion by macrophages stimulated with aldosterone promotes renal fibroblasts to a profibrotic phenotype

Wang

Zhang

et al. 2018

Int J Mol Med

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Macrophages have been identified as a key cell type in the pathogenesis of renal interstitial fibrosis (RIF). However, the mechanism through which macrophages drive fibrosis remains unclear. The current study focuses on the effects and possible underlying mechanism of allograft inflammatory factor-1 (AIF-1), an inflammation-responsive scaffold protein expressed and secreted by macrophages, in promoting fibroblasts to a profibrotic phenotype. In vivo experiments indicated that AIF-1, CD68 and α-smooth muscle actin (α-SMA) were upregulated in kidney tissues of mice subjected to unilateral ureteric obstruction, while their expressions were inhibited by an aldosterone receptor antagonist, spironolactone. Double immunofluorescence staining revealed that AIF-1 expression co-localized with CD68-positive macrophages in the renal interstitium, indicating that AIF-1 expression in macrophages was increased in the RIF animal model. Furthermore, to identify the role of AIF-1 in promoting fibrosis, its expression and secretion by the RAW264.7 macrophage cell line were detected in vitro. The expression levels of α-SMA, phosphorylated p38 (p-p38) and fibronectin (FN) in fibroblasts were examined subsequent to co-culture with macrophages. The increase in AIF-1 expression and secretion was confirmed in RAW264.7 cells in response to aldosterone. After 72 h of co-culture between fibroblasts and macrophages stimulated with aldosterone, the α-SMA expression was induced in fibroblasts, with significantly increased expression levels of FN and p-p38 observed. In addition, AIF-1 expression was reduced by stable transfection of RAW264.7 cells with AIF-1 small interfering RNA, resulting in significantly reduced expression levels of α-SMA, p-p38 and FN in fibroblasts co-cultured with macrophages as compared with normal macrophages. These findings indicate that the expression of AIF-1 in macrophages is critical for the activation of renal fibroblasts to a profibrotic phenotype. AIF-1 expression was upregulated in macrophages, and may be a novel mechanism linking macrophages to the promotion of RIF via the p38 signaling pathway.

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“…Biopsy samples of liver allografts 90 minutes after reperfusion demonstrate significant upregulation of genes in the allograft involved in activation and function of innate immune cells 17 . Similarly, elevated peripheral blood gene expression of the innate immune receptors toll-like receptor 2 and 4 (TLR2 and TLR4) measured 3 to 6 days after reperfusion is associated with delayed kidney graft function 18 . We identified significant differential expression of innate immune and inflammasome pathways in circulating cells within 2 hours of lung reperfusion, indicating that early damage to the allograft in the setting of ischemia reperfusion injury results in an extremely rapid recipient systemic response, likely in response to Damage Associated Molecular Patterns (DAMPs) released by the lung allograft.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Blood Gene Expression Changes Associated With Primary Graft Dysfunction After Lung Transplantation

Diamond

Cantu

Porteous

et al. 2017

American Journal of Transplantation

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Recipient responses to primary graft dysfunction (PGD) after lung transplantation may have important implications to the fate of the allograft. We therefore evaluated longitudinal differences in peripheral blood gene expression in subjects with PGD. RNA expression was measured throughout the first transplant year in 106 subjects enrolled in the Clinical Trials in Organ Transplantation-03 study using a panel of 100 hypothesis-driven genes. PGD was defined as grade 3 in the first 72 posttransplant hours. Eighteen genes were differentially expressed over the first year based on PGD development, with significant representation from innate and adaptive immunity genes, with most differences identified very early after transplant. Sixteen genes were overexpressed in the blood of patients with PGD compared to those without PGD within 7 days of allograft reperfusion, with most transcripts encoding innate immune/inflammasome-related proteins, including genes previously associated with PGD. Thirteen genes were underexpressed in patients with PGD compared to those without PGD within 7 days of transplant, highlighted by T cell and adaptive immune regulation genes. Differences in gene expression present within 2 hours of reperfusion and persist for days after transplant. Future investigation will focus on the long-term implications of these gene expression differences on the outcome of the allograft.

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Early Expression Profile of Inflammatory Markers and Kidney Allograft Status

Cited by 15 publications

References 10 publications

Over-Expression of Allograft Inflammatory Factor-1 (AIF-1) in Patients with Rheumatoid Arthritis

Over-Expression of Allograft Inflammatory Factor-1 (AIF-1) in Patients with Rheumatoid Arthritis

Upregulation of allograft inflammatory factor‑1 expression and secretion by macrophages stimulated with aldosterone promotes renal fibroblasts to a profibrotic phenotype

Peripheral Blood Gene Expression Changes Associated With Primary Graft Dysfunction After Lung Transplantation

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