AIF1: Function and Connection with Inflammatory Diseases

De Leon-Oliva, Diego; Garcia-Montero, Cielo; Fraile-Martinez, Oscar; Boaru, Diego Liviu; García-Puente, Luis; Rios-Parra, Antonio; Garrido-Gil, Maria J.; Casanova-Martín, Carlos; García-Honduvilla, Natalio; Bujan, Julia; Guijarro, Luis G.; Alvarez-Mon, Melchor; Ortega, Miguel A.

doi:10.3390/biology12050694

Cited by 17 publications

(10 citation statements)

References 196 publications

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“…The AIF-1 gene is situated in the MHC class III region, close to the TNF-α, TNF-β, and NF-κB, complement cascade protein genes, and surface glycoprotein genes [ 27 ]. The relevance of AIF-1 in multiple diseases has been demonstrated broadly [ 35 ]. AIF-1 exert a critical immunomodulatory action, boosting the expression of many inflammatory mediators and favor macrophage and vascular smooth muscle cell proliferation and migration [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Chronic Venous Disease during Pregnancy Is Related to Inflammation of the Umbilical Cord: Role of Allograft Inflammatory Factor 1 (AIF-1) and Interleukins 10 (IL-10), IL-12 and IL-18

Sánchez-Trujillo,

Fraile-Martinez,

García-Montero

et al. 2023

JPM

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Chronic venous disease (CVD) is a common condition that affects the veins in the lower limbs, resulting in a variety of symptoms, such as swelling, pain, and varicose veins (VVs). The plenty hormonal, hemodynamic and mechanical changes occurred in pregnancy make women especially vulnerable to suffer from this condition in this period. Previous works have identified that CVD is associated with an increased inflammatory milieu and significant damage in maternofetal tissues, such as the umbilical cord. However, the inflammatory status of this structure in these patients has not been studied yet. Thus, the aim of the present study was to examine gene and protein expression of a set of inflammatory markers—Allograft inflammatory factor 1 (AIF-1), the proinflammatory cytokines interleukin 12A (IL-12A) and IL-18 and the anti-inflammatory product IL-10—in the umbilical cord of women with CVD during pregnancy (N = 62) and healthy pregnant women (HC; N = 52) by the use of real time qPCR and immunohistochemistry (IHC). Our results demonstrate that the umbilical cord tissue from CVD women exhibit an increased expression of AIF-1, IL-12A and IL-18 along with a decrease in IL-10. Therefore, our study suggests an inflammatory status of this structure related to CVD. Further studies should be conducted to evaluate the expression of other inflammatory markers, as well as to analyze the maternofetal impact of these findings.

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Section: Discussionmentioning

confidence: 99%

Chronic Venous Disease during Pregnancy Is Related to Inflammation of the Umbilical Cord: Role of Allograft Inflammatory Factor 1 (AIF-1) and Interleukins 10 (IL-10), IL-12 and IL-18

Sánchez-Trujillo,

Fraile-Martinez,

García-Montero

et al. 2023

JPM

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“…These results suggest that germ cells in L1;L2;A mice may be preparing to enter meiosis before ongoing apoptosis (Figure S2). Enrichment score expression of macrophage scavenger reporter 1 (MSR1/ CD204), a macrophage marker 55 and of allograft inflammatory factor 1 (AIF1), a protein involved in the activation of macrophages, T lymphocytes and dendritic cells, 56 was observed in the testis of L1;L2;A mice (Figure 5D) further confirming the presence of a robust immune response.…”

Section: The Expression Levels Of Leydig Cell and Germ Cell Genes Are...mentioning

confidence: 73%

Lats1 and Lats2 regulate YAP and TAZ activity to control the development of mouse Sertoli cells

Abou Nader,

Charrier,

Meisnsohn

et al. 2024

The FASEB Journal

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Recent reports suggest that the Hippo signaling pathway regulates testis development, though its exact roles in Sertoli cell differentiation remain unknown. Here, we examined the functions of the main Hippo pathway kinases, large tumor suppressor homolog kinases 1 and 2 (Lats1 and Lats2) in developing mouse Sertoli cells. Conditional inactivation of Lats1/2 in Sertoli cells resulted in the disorganization and overgrowth of the testis cords, the induction of a testicular inflammatory response and germ cell apoptosis. Stimulated by retinoic acid 8 (STRA8) expression in germ cells additionally suggested that germ cells may have been preparing to enter meiosis prior to their loss. Gene expression analyses of the developing testes of conditional knockout animals further suggested impaired Sertoli cell differentiation, epithelial‐to‐mesenchymal transition, and the induction of a specific set of genes associated with Yes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ)‐mediated integrin signaling. Finally, the involvement of YAP/TAZ in Sertoli cell differentiation was confirmed by concomitantly inactivating Yap/Taz in Lats1/2 conditional knockout model, which resulted in a partial rescue of the testicular phenotypic changes. Taken together, these results identify Hippo signaling as a crucial pathway for Sertoli cell development and provide novel insight into Sertoli cell fate maintenance.

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“…AIF1 is known to induce the production of pro-inflammatory molecules, including the inflammatory factors IL-6 and TNF-α, and cause elevation of reactive oxygen species (ROS) ( 50 ). Furthermore, it has been shown that the role of AIF1 in macrophages is critical for maintaining their survival and promoting inflammatory activity ( 51 , 52 ). Based on these properties, it is reasonable to assume that there may be a positive correlation between AIF1 and AS, which is an immune-mediated disease characterized by chronic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Proteome-wide Mendelian randomization identifies therapeutic targets for ankylosing spondylitis

Zhao,

Fang,

Lai

et al. 2024

Front. Immunol.

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BackgroundAnkylosing Spondylitis (AS) is a chronic inflammatory disorder which can lead to considerable pain and disability. Mendelian randomization (MR) has been extensively applied for repurposing licensed drugs and uncovering new therapeutic targets. Our objective is to pinpoint innovative therapeutic protein targets for AS and assess the potential adverse effects of druggable proteins.MethodsWe conducted a comprehensive proteome-wide MR study to assess the causal relationships between plasma proteins and the risk of AS. The plasma proteins were sourced from the UK Biobank Pharma Proteomics Project (UKB-PPP) database, encompassing GWAS data for 2,940 plasma proteins. Additionally, GWAS data for AS were extracted from the R9 version of the Finnish database, including 2,860 patients and 270,964 controls. The colocalization analysis was executed to identify shared causal variants between plasma proteins and AS. Finally, we examined the potential adverse effects of druggable proteins for AS therapy by conducting a phenome-wide association study (PheWAS) utilizing the extensive Finnish database in version R9, encompassing 2,272 phenotypes categorized into 46 groups.ResultsThe findings revealed a positive genetic association between the predicted plasma levels of six proteins and an elevated risk of AS, while two proteins exhibited an inverse association with AS risk (Pfdr < 0.05). Among these eight plasma proteins, colocalization analysis identified AIF1, TNF, FKBPL, AGER, ALDH5A1, and ACOT13 as shared variation with AS(PPH3+PPH4>0.8), suggesting that they represent potential direct targets for AS intervention. Further phenotype-wide association studies have shown some potential side effects of these six targets (Pfdr < 0.05).ConclusionOur investigation examined the causal connections between six plasma proteins and AS, providing a comprehensive understanding of potential therapeutic targets.

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AIF1: Function and Connection with Inflammatory Diseases

Cited by 17 publications

References 196 publications

Chronic Venous Disease during Pregnancy Is Related to Inflammation of the Umbilical Cord: Role of Allograft Inflammatory Factor 1 (AIF-1) and Interleukins 10 (IL-10), IL-12 and IL-18

Chronic Venous Disease during Pregnancy Is Related to Inflammation of the Umbilical Cord: Role of Allograft Inflammatory Factor 1 (AIF-1) and Interleukins 10 (IL-10), IL-12 and IL-18

Lats1 and Lats2 regulate YAP and TAZ activity to control the development of mouse Sertoli cells

Proteome-wide Mendelian randomization identifies therapeutic targets for ankylosing spondylitis

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