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

Abstract

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.

The Role of AIF-1 in the Aldosterone-Induced Vascular Calcification Related to Chronic Kidney Disease: Evidence From Mice Model and Cell Co-Culture Model

“…Previous studies showed that inhibition of AIF-1 protein expression in ECs and VSMCs could alleviate atherosclerosis ( 28 – 30 ). And mononuclear macrophage hyperactivation and VSMCs trans-differentiation were observed in AIF-1 over-expressed mice ( 31 ). Therefore, AIF-1 is an important inflammatory regulatory factor, which is involved in regulating vascular calcification via both ECs and VSMCs.…”

AIF-1, a potential biomarker of aggressive tumor behavior in patients with non-small cell lung cancer

“…A higher degree of CD68 + macrophage infiltration is associated with poor prognosis of different types of cancer, including NSCLC [ 37 – 39 ]. AIF-1 has been found to co-localize with CD68 + macrophages in human atherosclerotic coronary arteries, renal interstitium, and synovial membrane, being considered a marker of activated macrophages and endowed with prognostic value for inflammation-related diseases including cancer [ 38 , 40 , 41 ]. Taken together, our results indicate that AIF-1 is expressed in macrophages that infiltrate NSCLC tissue and that higher AIF-1 expression is associated with more aggressive behavior of cancer.…”

Exosomal lincRNA-p21/AIF-1 promoted inflammation of human tubular epithelial cell via CMPK2/NLRP3 pathway in urate nephropathy

“…On the other hand, allograft in ammatory factor 1 (AIF-1) is a calcium-binding cytoplasmic scaffold protein observed in several in ammatory diseases, including atherosclerosis, rheumatoid arthritis, renal tubulointerstitial brosis, vascular calci cation, and diabetic kidney disease [15,16,17,18,19]. Our group has conducted a series of studies on AIF-1 and con rmed its role in promoting in ammation and brosis in the renal tubulointerstitium.…”