Allograft Inflammatory Factor-1 Gene Research Articles

Inhibition of AIF-1 alleviates laser-induced macular neovascularization by inhibiting endothelial cell proliferation via restrained p44/42 MAPK signaling pathway

Age-related macular degeneration (AMD) is a leading blinding disease worldwide, and macular neovascularization (MNV) is a common complication encountered in the advanced stages of AMD. While the underlying causes of MNV remain elusive, aberrant multiplication of choroidal endothelial cells (CECs) and increased vascular endothelial growth factor (VEGF) are thought to play significant roles in the occurrence and development of MNV. Allograft inflammatory factor-1(AIF-1) is a crucial regulatory factor of vascular tubular structure formation and growth, involving the proliferation and migration of vascular endothelial cells and various tumor cells. This study aimed to understand how AIF-1 effects the proliferation of CECs and the subsequent progression of MNV. To study this, a mouse MNV model was established through laser injury, and the AIF-1 expression levels were then measured using western blot and immunohistochemistry. AIF-1 siRNA was intravitreally injected to silence AIF-1 gene expression. Western blot and choroidal flat mount were performed to measure the progression of MNV and proliferation of the CECs. These results showed that the protein expression of AIF-1 was significantly elevated in the laser-induced mouse MNV model, and the expression trend was consistent with VEGF. The protein level of AIF-1 was significantly decreased after the intravitreal injection of AIF-1 siRNA, the damage range of laser lesions was significantly reduced, and the proliferation of endothelial cells was inhibited. Knockdown of the AIF-1 gene significantly inhibited the expression of mitogen-activated protein kinase p44/42 in MNV lesions. In summary, this research demonstrates that AIF-1 promoted MNV progression by promoting the proliferation of CECs and that silencing AIF-1 significantly ameliorates MNV progression in mouse models, which may act through the p44/42 MAPK signaling pathway. AIF-1 could be a new potential molecular target for MNV.

The Effect of Allograft Inflammatory Factor-1 on Inflammation, Oxidative Stress, and Autophagy via miR-34a/ATG4B Pathway in Diabetic Kidney Disease.

Increasing evidence suggests that disorders of inflammation, oxidative stress, and autophagy contribute to the pathogenesis of diabetic kidney disease (DKD). This study attempted to clarify the effect of allograft inflammatory factor-1 (AIF-1), miR-34a, and ATG4B on inflammation, oxidative stress, and autophagy in DKD both in vitro and in vivo experiments. In vivo, it was found that the levels of AIF-1, miR-34a, oxidative stress, and inflammatory factors were significantly increased in blood and urine samples of DKD patients and mouse models and correlated with the level of urinary protein. In vitro, it was also found that the expressions of AIF-1, miR-34a, ROS, and inflammatory factors were increased, while ATG4B and other autophagy related proteins were decreased in human renal glomerular endothelial cells (HRGECs) cultured with high concentration glucose medium (30 mmol/L). When AIF-1 gene was overexpressed, the levels of miR-34a, ROS, and inflammatory factors were significantly upregulated, and autophagy-related proteins such as ATG4B were downregulated, while downregulation of AIF-1 gene had the opposite effect. In addition, miR-34a inhibited the expression of ATG4B and autophagy-related proteins and increased the levels of ROS and inflammation. Furthermore, the result of luciferase reporter assay suggested that ATG4B was the target gene of miR-34a. When ATG4B gene was overexpressed, the level of autophagy was upregulated, and inflammatory factors were downregulated. Conversely, when ATG4B gene was inhibited, the level of autophagy was downregulated, and inflammatory factors were upregulated. Then, autophagy inducers inhibited the levels of inflammation and ROS, whereas autophagy inhibitors had the opposite function in HRGECs induced by glucose (30 mmol/L). In conclusion, the above data suggested that AIF-1 regulated the levels of inflammation, oxidative stress, and autophagy in HRGECs via miR-34a/ATG4B pathway to contribute to the pathogenesis of diabetic kidney disease.

Association of snps of aif-1 gene with susceptibility to oral cancer in chinese population

Abstract To investigate the association between allograft inflammatory factor-1 (AIF-1) gene polymorphism and susceptibility to oral cancer in Chinese population. A case-control study was conducted to collect 400 cases of newly diagnosed oral cancer patients diagnosed by pathology from January 2015 to June 2019 and 400 cases of physical examination in the same period. Single nucleotide polymorphisms (SNPs) of the AIF-1 gene were detected using TaqMan probe technology. Unconditional logistic regression analysis was used to calculate the odd ratios (OR) and 95% confidence interval (CI) of the association between AIF-1 gene polymorphism and oral cancer susceptibility. GG genotypes reduced the risk of oral cancer in co-dominant models (OR = 0.499, 95% CI: 0.328-0.760, P = 0.001) and recessive models (OR = 0.496, 95% CI: 0.342-0.729, P < 0.001). There was no significant difference between the case group and the control group in the dominant model genotype (OR = 0.836, 95% CI: 0.623~1.121, P = 0.836). Conclusion AIF-1 gene rs2857595 gene SNPs can reduce the risk of oral cancer.

IMMU-29. AIF1 IS A PROGNOSTIC BIOMARKER AND CORRELATED WITH IMMUNE INFILTRATES IN GLIOMAS

Gliomas remain highly variable clinical behaviors, leading to emerging studies to identify prognostic factors. AIF1 (Allograft Inflammatory Factor 1) is critical for promoting both macrophage- and dendritic cells (DCs)-mediated inflammatory response and growth of vascular smooth muscle cells and T-lymphocytes. Through comparative analyses of primary LGG patients from The Cancer Genome Atlas (TCGA) dataset and Chinese Glioma Genome Atlas(CGGA) dataset, we reported that the expression level and methylation level of AIF1 gene vary among glioma patients and AIF1 expression or gene body methylation is significantly associated with glioma patient survival. Cox regression results confirmed that AIF1 played an independent predictor of survival in lower-grade glioma(LGG), with a cox coefficient of 0.251 indicating a worse prognosis. Moreover, AIF1 expression was positively correlated with infiltrating levels of CD4+ T and B cells, macrophages, neutrophils, and DCs in LGG and glioblastoma(GBM). AIF1 expression also showed strong correlations with specific immune cell markers in LGG and GBM. In addition, AIF1 expression potentially contributed to the regulation of glioma-associated macrophages and microglia. In conclusion, our findings suggested that AIF1 was correlated with prognosis and immune infiltrating levels, and it can be used as a prognostic factor in gliomas.

Allograft Inflammatory Factor AIF-1: early immune response in the Mediterranean sea urchin Paracentrotus lividus

Echinoderms are a phylum of deuterostomic invertebrates that play a key role in maintaining the biodiversity of marine ecosystems. They represent a good study model for immunity because their coelomic fluid contains different types of cells involved in the inflammatory response: the coelomocytes. In the case of the sea urchin Paracentrotus lividus, the coelomocyte population is mainly represented by amoebocytes and uncoloured spherulocytes that implement a defence program through phagocytosis, encapsulation, cytotoxicity, and production of antimicrobial agents.The purpose of this study was to find evidence of a possible modulating effect of lipopolysaccharide LPS on the expression of the AIF-1 gene and therefore to determine whether or not there is a correlation between the P. lividus immune response and the expression of this gene when the homeostasis of the animals is disturbed by a bacterial infection which, in this case, was simulated with treatment with LPS. AIF-1 (Allograft Inflammatory Factor 1) is a 17 kDa calcium-binding protein that, in vertebrates, is involved in the activation of macrophages.Similarly, in Echinoids and in general in invertebrates, the expression of this gene increases considerably after a bacterial attack and this suggests that it plays a key role during the immune responses.

AIF-1 gene does not confer susceptibility to Behçet's disease: Analysis of extended haplotypes in Sardinian population.

BackgroundBehçet’s disease (BD) is a polygenic immune-mediated disorder characterized by a close association with the HLA-B*51 allele. The HLA region has a strong linkage disequilibrium (LD) and carries several genetic variants (e.g. MIC-A, TNF-α genes) identified as associated to BD because of their LD with HLA-B*51. In fact, the HLA-B*51 is inherited as part of extended HLA haplotypes which are well preserved in patients with BD. Sardinian population is highly differentiated from other Mediterranean populations because of a distinctive genetic structure with very highly preserved HLA haplotypes.Patients and methodsIn order to identify other genes of susceptibility to BD within the HLA region we investigated the distribution of human Allograft Inflammatory Factor-1 (AIF-1) gene variants among BD patients and healthy controls from Sardinia. Six (rs2736182; rs2259571; rs2269475; rs2857597; rs13195276; rs4711274) AIF-1 single nucleotide polymorphisms (SNPs) and related extended haplotypes have been investigated as well as their LD within the HLA region and with HLA-B*51. Overall, 64 BD patients, 43 HLA-B*51 positive healthy controls (HC) and 70 random HC were enrolled in the study.ResultsHLA-B*51 was the only allele with significantly higher frequency (pc = 0.0021) in BD patients (40.6%) than in HC (9.8%). The rs2259571T AIF-1 variant had a significantly reduced phenotypic, but not allelic frequency in BD patients (72.1%; pc = 0.014) compared to healthy population (91.3%). That was likely due to the LD between HLA-B*51 and rs2259571G (pc = 9E-5), even though the rs2259571G distribution did not significantly differ between BD patients and HC.ConclusionNo significant difference in distribution of AIF-1 SNPs haplotypes was observed between BD patients and HC and between HLA-B*51 positive BD patients and HLA-B*51 positive HC. Taken together, these results suggest that AIF-1 gene is not associated with susceptibility to BD in Sardinia.

AIF1 Gene RS2269475:C&gt;T Polymorphism is Associated With Rheumatoid Arthritis Development but not With Disease Activity

Objectives: This study aims to examine whether the allograft inflammatory factor-1 (AIF1) gene rs2269475:C>T polymorphism is associated with rheumatoid arthritis (RA) susceptibility, and whether this polymorphism influences disease activity in patients with RA. Patients and methods: We examined 380 patients (62 males, 318 females; mean age 58.1±12.9 years; range 20 to 78 years; age at disease onset 47.4±13.5 years) with RA diagnosed according to the criteria of American College of Rheumatology and 378 healthy control subjects (126 males, 252 females; mean age 69.6±12.1 years; range 21 to 75 years). Disease activity score in 28 joints (DAS28) was calculated. The active form of RA was diagnosed when DAS28 was >2.5, the non-active form was diagnosed when DAS28 was ≤2.5. Results: The frequency of TT genotype was significantly higher in RA patients compared with the controls (TT vs. CT+CC: odds ratio=6.22, 95% confidence interval: 1.82-21.28; p=0.0013). The frequency of T allele was 18.55% among RA patients and 12.04% among healthy subjects (odds ratio=1.67, 95% confidence interval=1.25-2.21; p=0.00046). There were no statistically significant differences in distribution of genotypes and alleles between patients with active and non-active disease (DAS28 >2.5 and ≤2.5, respectively). Conclusion: The results of present study suggest that AIF1 gene rs2269475 polymorphism is associated with RA development; however, has no influence on disease activity.

Cloning and gene expression of allograft inflammatory factor-1 (AIF-1) provide new insights into injury and bacteria response of the sea cucumber Apostichopus japonicus (Selenka, 1867)

Allograft inflammatory factor-1 (AIF-1) is an interferon (IFN)-γ-inducible Ca2+-binding cytokine that associates with the immune defense and inflammatory response. In this study, we reported AIF-1 gene in sea cucumber Apostichopus japonicus (AjAIF-1). The full-length cDNA of AjAIF-1 is 1541 bp with an open reading frame (ORF) of 477 bp encoding 158 amino acids. Two EF-hand Ca2+-binding motifs were found in the deduced AjAIF-1. AjAIF-1 was widely expressed in all tested tissues (body wall, intestine, respiratory tree, tube feet, coelomocytes and longitudinal muscle), with the highest expression in respiratory tree. After Vibrio splendidus challenge and physical injury, AjAIF-1 transcripts were significantly upregulated in coelomocytes. The mRNA expression level of AjAIF-1 in coelomocytes reached to the highest value at 4 h (3.38-folds vs. the PBS control, P < 0.05) post injection. After papilla injury, the mRNA level of AjAIF-1 in coelomocytes was upregulated, and its peak value was found at 4 h (3.88-folds vs. the control, P < 0.05). These results indicated that 1) AjAIF-1 sensitively responds to pathogen infection; 2) AjAIF-1 is involved in acute inflammatory response. Our findings gain general information about the role of AjAIF-1 in the innate immunity of A. japonicus.

Influence of Cyclooxygenase-2 (COX-2) gene promoter-1195 and allograft inflammatory factor-1 (AIF-1) polymorphisms on allograft outcome in Hispanic kidney transplant recipients

Cyclooxygenase-2 (COX-2) alleles have been associated with allograft outcomes in kidney transplant recipients; however, these alleles may be in linkage with other genes. Human allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein and is produced by macrophages. Its synthesis is regulated by several cytokines, including interferon gamma. We investigated whether polymorphisms of gene encoding COX-2 and AIF-1 were associated with allograft outcomes among Hispanic renal transplant recipients (RTRs). A total of 527 de novo RTRs of Hispanic ethnicity were included in this study transplanted at St. Vincent Medical Center (SVMC) during 2000-2009. Patients were genotyped for the following: COX-2 (-1195C>T rs689466, intron 6 rs2066826) and AlF1 (rs2269475). Analysis of the results showed that COX-2-1195 CC genotype (OR=1.92, CI%=1.00-3.67, p=0.04) were more frequent, but COX-2-1195 CT genotype was less frequent in kidney allograft acute rejection in comparison with control group (OR=0.59, CI%=0.38-0.91, p=0.017). The genetic variant TT/CT of the AIF-1 gene was associated with a lower risk of rejection (OR=0.63, CI%=0.41-0.98, p=0.038). No association of COX-2 (rs2066826) was observed with allograft rejection. We are unable to find statistically significant association between COX-2 and AIF-1 gene polymorphisms and allograft survival. The -1195C>T in the COX-2 promoter and AIF-1 gene polymorphisms could be a potential predictor of allograft rejection in our Hispanic kidney transplant recipients.

Expression of allograft inflammatory factor-1 (AIF-1) in response to bacterial challenge and tissue injury in the pearl oyster, Pinctada martensii

Allograft inflammatory factor-1 (AIF-1), an interferon (IFN)-γ-inducible calcium-binding cytokine, is associated with the inflammatory response and defense. We cloned and analyzed the expression pattern of the AIF-1 gene of the pearl oyster Pinctada martensii, hereafter designated PmAIF-1. The full-length PmAIF-1 cDNA is 946bp in length and consists of a 5′-untranslated region (UTR) of 120bp, a 3′-UTR of 376bp, and an open reading frame (ORF) of 450bp encoding a polypeptide of 149 amino acids with an estimated molecular mass of 17kDa. Sequence analysis reveals that PmAIF-1 contains two EF hand Ca+2-binding motifs like those in previously characterized AIF-1s while alignment with known AIF-1 protein sequences reveals higher similarity to invertebrate orthologs than to those of vertebrates.Quantitative PCR analysis reveals that PmAIF-1 is constitutively expressed, with the highest expression detected in hemocytes, and the expression level of PmAIF-1 mRNA was significantly up-regulated in hemocytes, gill, digestive gland under bacterial challenge and tissue injury. After challenged by gram-negative bacteria Vibrio alginolyticus and Vibrio parahaemolyticus, gram-positive bacteria Bacillus subtilis, the expression level of this gene in hemocytes were all up-regulated and reached the maximum point at 12h (5.80 folds, P<0.01), 6h (5.02 folds, P<0.01) and 12h (5.49 folds, P<0.01), respectively. Under shell damage and mantle injury, PmAIF-1 mRNA increased gradually in the first 3h and reached a peak of expression at 6h post-injury. These findings suggest that PmAIF-1 is an acute-response protein involved in the innate immune responses of pearl oysters, and provide general information about the mechanisms of innate immune defense against bacterial infection in pearl oysters.

AIF-1 Gene Expression and Polymorphism in Association with Cardiac Allograft Rejection

Long- term clinical outcomes after cardiac transplantation still remains a challenge because of rejection episodes and the development of coronary vasculopathy. Rejection episode (RE) is a complex immunologic response, associated with the inflammatory signaling network. Allograft inflammatory factor-1 (AIF-1) has an important role in inflammatory process associated with transplantation. The goal was to demonstrate an association between the AIF-1 gene expression and genotype variation with RE. Peripheral blood and endomyocardial specimens were tested by semi-quantitative RT-PCR and immunohistochemistry (IHC) stains for identification of AIF-1 and IL-18 and were analyzed against clinical ISHLT grades for rejection. Sequence-specific primers for AIF-1 gene polymorphism were used to determine the C or the T allele variation in association with RE. The prevalence of CT heterozygous alleles were found significantly higher in patients who were presented with (0) RE during the first 6 months after transplantation as compared with CC alleles. The correlation of having CT alleles versus CC were inversely distributed with the increase in the number of RE. The isoform 2 expression was almost 2-fold higher than isoform 1 or isoform 3 in specimens with grade 3A RE versus specimens with grade 0-1 RE (p<0.001). The AIF-1 and the IL-18 were present in CMCs and in most of the MNCs in the specimens with grade 3A RE. The AIF-1 mRNA transcript expression was increased 5-fold in the biopsy specimens and it was1.7-fold higher than in peripheral blood monocytes in grade 3A RE. The IL-18 expression was increased 4.2-fold in biopsy specimens presented with 3A versus grade 0 (N) RE. Individuals with AIF-1 CC alleles are at a greater risk of developing the early rejection episodes. AIF-1 could serve as a suitable biomarker to monitor cardiac allograft RE through a less invasive procedure.

An allograft inflammatory factor 1 (AIF1) single nucleotide polymorphism (SNP) is associated with anticentromere antibody positive systemic sclerosis

To identify genetic associations between allograft inflammatory factor 1 (AIF1) and systemic sclerosis (SSc), or its subsets, using a single nucleotide polymorphism (SNP) in a replicate case-control study. The frequencies of alleles and genotypes of an SNP, rs2269475, for the AIF1 gene were examined in two large independent cohorts of SSc patients (n = 1015 total), and compared with two groups of normal controls (n = 893 total). Both cases and controls were stratified by ethnicity (Caucasian, African American and Hispanic) and by autoantibody status [anti-centromere antibodies (ACA) and anti-topoisomerase I antibody (ATA)]. The minor T allele and CT/TT genotype frequencies of the AIF1 SNP were not observed more frequently in SSc patients of the three ethnic groups (individually or combined) when compared with controls. On the other hand, T and CT/TT frequencies were significantly increased in ACA-positive Caucasian SSc patients, and all ACA-positive SSc patients (the three ethnic groups combined), when compared with ACA-negative SSc patients and with normal controls, with odds ratios of approximately 1.5. The data demonstrate a genetic association between AIF1 and the ACA-positive subset of SSc. This polymorphism is a non-synonymous substitution and therefore likely to represent an important functional change in AIF1. Since vascular pathology is a prominent feature in ACA-positive SSc patients, the observed association with a vasculotrophic inflammatory gene is biologically plausible and warrants further research.

Functional Molecular Biodiversity: Assessing the Immune Status of Two Sponge Populations (Suberites domuncula) on the Molecular Level

Abstract. Porifera (sponges) are sessile filter feeders living primarily in the marine environment. In this study the population diversity of one species, the demosponge Suberites domuncula, has been investigated in an isolated area, the Limski Canal (LC) near Rovinj (Croatia; Mediterranean Sea), in comparison to that in the open sea (OS), only 10–20 km apart from the LC. The immune competence of the S. domuncula specimens was studied in response to exposure to the bacterial endotoxin LPS. The level of phosphorylation of the p38 kinase from specimens collected in LC is significantly lower than that of OS animals. To confirm the biochemical data on the molecular level, the technique of identification of the differentially expressed transcripts in specimens from OS versus LC was applied. Most of the differently expressed transcripts coded for the allograft inflammatory factor‐1 (AIF‐1), a molecule involved in self‐self/self‐non‐self recognition also in S. domuncula. The level of gene expression of the AIF‐1 gene, determined by Northern blotting and quantitative ‘real‐time Q‐PCR’ revealed much higher values in the OS animals. Moreover, the degree of polymorphism in the AIF‐1 and in the adjacent tubulin locus was high in animals from both locations. Populations of S. domuncula therefore comprise a high genetic diversity even in closely located areas. This finding has prompted long‐term research activities in the Limski Canal, a defined marine protected area.

TNF, TNF receptor type 1, and allograft inflammatory factor-1 gene polymorphisms in Japanese patients with type 1 diabetes

The human leukocyte antigen (HLA) class III region, located on chromosome 6p21, has been regarded as one of the susceptible loci for type 1 diabetes. Because it contains many genes related to inflammatory and immune responses, including tumor necrosis factor (TNF), lymphotoxin-α (LT-α), and allograft inflammatory factor 1 (AIF-1) genes, it is unclear which gene within the class III region is responsible for the susceptibility to the disease. We sequenced the AIF-1 gene region and detected three novel polymorphisms, all of which were diallelic and localized at introns. Then, we investigated AIF-1, TNF, and LT-α gene polymorphisms in 165 patients with type 1 diabetes, consisting of 90 patients with young-onset type 1 diabetes, 75 patients with adult-onset type 1 diabetes, and 200 control patients. We also analyzed TNF receptors type 1 (TNFR1) and type 2 (TNFR2) gene polymorphisms, located on chromosome 12p13 and 1p36, respectively. Although there were significant differences between type 1 diabetes patients and controls in the distributions of TNF promoter polymorphisms at position −1031 and −857, and LT-α gene NcoI polymorphism, none of them was independently associated with the disease after two-locus analysis with HLA class II alleles. We detected the significantly increased frequency of the −383C allele, located in the TNFR-1 promoter region, in both young-onset and adult-onset diabetes patients compared with controls. In addition, the −383C allele was found to be associated with higher expression of the TNFR1 gene than that of −383A allele in in vitro expression. These results suggest that the TNFR1 gene region might be a susceptible locus to type 1 diabetes in Japanese.

DNA cloning and characterization of an allograft inflammatory factor-1 homologue in red sea bream ( Chrysophrys major)

We isolated allograft inflammatory factor-1 (AIF-1) homologue cDNA from lipopolysaccharide (LPS)-stimulated red sea bream leukocytes. We then determined that this cDNA encodes 444 bp in length and has an open reading frame that encodes 142 amino acids. The deduced amino acid sequence was homologous to the AIF-1s in carp and mammals (>65.5% sequence identity). The nucleotide sequence of the protein-coding region in the AIF-1 gene was determined to have six exons and five introns. The exon–intron structure resembles those of the mouse and the human. Genomic Southern blot analysis revealed the presence of a single AIF-1 gene per haploid in red sea bream. A time course evaluation indicated that the expression level of AIF-1 gene in LPS-stimulated leukocytes was static in the first hour, but gradually increased from 3 to 24 h. The similarities between AIF-1s in mammals and red sea bream suggest that the AIF-1 in red sea bream may have a similar function in activated leukocytes as AIF-1s do in mammals.