TNFAIP3-interacting Protein Research Articles

TNFAIP3-interacting protein 1 polymorphisms and their association with symptomatic human respiratory syncytial virus infection and bronchiolitis in infants younger than one year from South Africa: A case-control study

ObjectivesThis study analyzed the association of TNFAIP3-interacting protein 1 (TNIP1) polymorphisms with the symptomatic human respiratory syncytial virus (HRSV) infection and bronchiolitis in infants. MethodsA case-control study was conducted involving 129 hospitalized infants with symptomatic HRSV infection (case group) and 161 healthy infants (control group) in South Africa (2016-2018). Six TNIP1 polymorphisms (rs869976, rs4958881, rs73272842, rs3792783, rs17728338, and rs999011) were genotyped. Genetic associations were evaluated using logistic regression adjusted by age and gender. ResultsBoth rs73272842 G and rs999011 C alleles were associated with reduced odds for symptomatic HRSV infection (adjusted odd ratio [aOR] = 0.68 [95% confidence interval {CI} = 0.48-0.96] and aOR = 0.36 [95% CI = 0.19-0.68], respectively] and bronchiolitis (aOR = 0.71 [95% CI = 0.50-1.00] and aOR = 0.38 [95% CI = 0.22-0.66], respectively). The significance of these associations was validated using the BCa Bootstrap method (P <0.05). The haplotype GC (composed of rs73272842 and rs999011) was associated with reduced odds of symptomatic HRSV infection (aOR = 0.53 [95% CI = 0.37-0.77]) and bronchiolitis (aOR = 0.62 [95% CI = 0.46-0.84]), which were validated by the BCa Bootstrap method (P = 0.002 for both). ConclusionTNIP1 rs73272842 G allele and rs999011 C allele were associated with reduced odds of symptomatic HRSV infection and the development of bronchiolitis in infants, suggesting that TNIP1 polymorphisms could impact susceptibility to HRSV illness.

TNIP2 inhibits amyloidogenesis by regulating the 3′UTR of BACE1: An in vitro study

TNFAIP3-interacting protein 2 (TNIP2) is known as a negative regulator of NF-κB signaling and inhibit inflammatory response and apoptosis, and is also involved in RNA metabolism. In this study, we investigated the potential role of TNIP2 in amyloidogenesis critically associated with Alzheimer’s disease (AD). We found a significant decline of TNIP2 protein level in both mouse and cell model of AD. In SH-SY5Y and HEK cells that stably express human full-length APP695 (SY5Y-APP and HEK-APP), TNIP2 overexpression decreased the protein levels of β-secretase (BACE1) and C99, as well as Aβ peptides (including Aβ40 and Aβ42), while those of α-secretase (ADAM10) and the related C83 remained unchanged. We further found that TNIP2 promoted the degradation of BACE1 mRNA and was able to bound to the 3′ untranslated region (3′UTR) with the reduced luciferase activity. These results indicated that TNIP2 effectively inhibited amyloidogenic processing by regulating the 3′UTR-associated mRNA decay of BACE1.

TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1.

Limitation of excessive inflammation due to selective degradation of pro-inflammatory proteins is one of the cytoprotective functions attributed to autophagy. In the current study, we highlight that selective autophagy also plays a vital role in promoting the establishment of a robust inflammatory response. Under inflammatory conditions, here TLR3-activation by poly(I:C) treatment, the inflammation repressor TNIP1 (TNFAIP3 interacting protein 1) is phosphorylated by Tank-binding kinase 1 (TBK1) activating an LIR motif that leads to the selective autophagy-dependent degradation of TNIP1, supporting the expression of pro-inflammatory genes and proteins. This selective autophagy efficiently reduces TNIP1 protein levels early (0-4 h) upon poly(I:C) treatment to allow efficient initiation of the inflammatory response. At 6 h, TNIP1 levels are restored due to increased transcription avoiding sustained inflammation. Thus, similarly as in cancer, autophagy may play a dual role in controlling inflammation depending on the exact state and timing of the inflammatory response.

Myelin oligodendrocyte glycoprotein-associated disease is associated with BANK1, RNASET2 and TNIP1 polymorphisms

AimHere we aimed to compare association of common immune-related genetic variants with three autoimmune central nervous system (CNS) demyelinating diseases, namely myelin oligodendrocyte glycoprotein-associated disease (MOGAD), multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MethodsIn this retrospective cross-sectional study, 26 common immune-related single nucleotide polymorphisms were genotyped in 102 patients with MOGAD, 100 patients with MS, 198 patients with NMOSD and 541 healthy control subjects recruited from Guangzhou, China. ResultsAmong all tested genetic variations, one polymorphism, B cell scaffold protein with ankyrin repeats 1 (BANK1) rs4522865 was associated with multiple disorders, namely MOGAD (OR = 1.94, 95% CI:1.19–3.17, P = 0.0059) and NMOSD (OR = 1.69, 95% CI:1.17–2.45). Besides BANK1 rs4522865, two other non-HLA loci, ribonuclease T2 (RNASET2) rs9355610 (OR = 0.47, 95% CI: 0.26–0.85) and TNFAIP3 interacting protein 1 (TNIP1) rs10036748 (OR = 1.76, 95% CI: 1.16–2.71), were associated with MOGAD. In addition, NMOSD was associated with signal transducer and activator of transcription 4 (STAT4) rs7574865 (OR = 1.58, 95% CI: 1.12–2.24) and general transcription factor Iii (GTF2I) rs73366469 (OR = 1.60, 95% CI:1.12–2.29), while MS was associated with a killer cell lectin like receptor G1 (KLRG1) rs1805673 (OR = 0.61, 95% CI: 0.40–0.94) and T-box transcription factor 21 (TBX21) rs17244587 (OR = 2.25, 95% CI: 1.25–4.06). ConclusionThe current study suggests for the first time three non-HLA susceptibility loci for MOGAD. In addition, comparison of association of 26 immune-related polymorphisms with three autoimmune CNS demyelinating diseases demonstrates substantial difference in genetic basis of those disorders.

Coilin as a regulator of NF-kB mediated inflammation in preeclampsia.

ABSTRACTThe nuclear factor-Kappa B (NF-κB) pathway is a crucial mediator of inflammatory signaling. Aberrant activation of NF-κB is associated with several disorders including preeclampsia (PE). Many regulators of the NF-κB pathway have been identified, including microRNAs (miRNAs). Specifically, miR-517-3p targets mRNA encoding TNFAIP3 Interacting Protein 1 (TNIP1), an inhibitor of NF-κB signaling. Activation of NF-κB increases production of the cytokine TNF superfamily member 15 (TNFSF15), leading to the upregulation of anti-angiogenic soluble vascular endothelial growth factor receptor 1 (sFlt-1). We have previously observed that Cajal bodies (CBs), subnuclear domains, are associated with the chromosome 19 miRNA gene cluster (C19MC), which encodes miR-517-3p. We have also found that coilin, the CB marker protein, is a positive regulator of miRNA biogenesis. Here we report that coilin is a regulator of miR-517-3p, sFlt-1, TNIP1, TNFSF15 and NF-κB activation, and this regulation is influenced by hypoxia. We also report that coilin and CBs are induced in the reduced uterine perfusion pressure (RUPP) rat model of PE. Collectively, the data presented here implicate coilin as a novel regulator of NF-κB activation and sFlt-1 upregulation.

Neuroprotective Function of TNFAIP3 Interacting Protein 2 Against Oxygen and Glucose Deprivation/Reoxygenation-Induced Injury in Hippocampal Neuronal HT22 Cells Through Regulation of the TLR4/MyD88/NF-κB Pathway.

BackgroundTumor necrosis factor-α (TNF-α)-induced protein 3-interacting protein 2 (TNIP2) has been well demonstrated to act as a principal contributor to the development of inflammatory diseases; however, the role of TNIP2 in cerebral ischemic/reperfusion injury has never been studied.MethodsGene expression was examined by using quantitative real-time polymerase chain reaction and Western blot. The functional role of TNIP2 in oxygen and glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury was evaluated using cell counting kit-8, terminal deoxynucleotidyl transferase dutp nick end labeling assay and enzyme-linked immunosorbent assay. Commercial kits were applied to evaluate the activity of NF-kappa-B (NF-κB) and caspase-3, as well as the release of lactate dehydrogenase release (LDH).ResultsTNIP2 expression was substantially declined in HT22 cells following OGD/R stimulation. TNIP2 overexpression attenuated ODG/R-induced inflammation in HT22 cells, as evidenced by reduced levels of TNF-α, interleukin (IL)-1β, and intercellular cell adhesion molecule-1 (ICAM-1), and increased levels of IL-10. TNIP2 overexpression also reduced activity of NF-κB under ODG/R condition. Meanwhile, OGD/R treatment caused a reduction of cell viability and an elevation of cell apoptosis in HT22 cells, as indicated by the increase in LDH and caspase-3 activity. Whereas, OGD/R-induced HT22 cell injury was mitigated by TNIP2 overexpression in HT22 cells. Besides, we found the involvement of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/NF-κB pathway in the neuroprotective effect of TNIP2 on OGD/R-induced HT22 cell damage.ConclusionTNIP2 overexpression mitigates OGD/R-induced inflammatory response and apoptosis. Moreover, TLR4/MyD88/NF-κB pathway participates in the protective effect of TNIP2 on OGD/R-induced neuronal damage.

The Anti-Inflammatory Protein TNIP1 Is Intrinsically Disordered with Structural Flexibility Contributed by Its AHD1-UBAN Domain.

TNFAIP3 interacting protein 1 (TNIP1) interacts with numerous non-related cellular, viral, and bacterial proteins. TNIP1 is also linked with multiple chronic inflammatory disorders on the gene and protein levels, through numerous single-nucleotide polymorphisms and reduced protein amounts. Despite the importance of TNIP1 function, there is limited investigation as to how its conformation may impact its apparent multiple roles. Hub proteins like TNIP1 are often intrinsically disordered proteins. Our initial in silico assessments suggested TNIP1 is natively unstructured, featuring numerous potentials intrinsically disordered regions, including the ABIN homology domain 1-ubiquitin binding domain in ABIN proteins and NEMO (AHD1-UBAN) domain associated with its anti-inflammatory function. Using multiple biophysical approaches, we demonstrate the structural flexibility of full-length TNIP1 and the AHD1-UBAN domain. We present evidence the AHD1-UBAN domain exists primarily as a pre-molten globule with limited secondary structure in solution. Data presented here suggest the previously described coiled-coil conformation of the crystallized UBAN-only region may represent just one of possibly multiple states for the AHD1-UBAN domain in solution. These data also characterize the AHD1-UBAN domain in solution as mostly monomeric with potential to undergo oligomerization under specific environmental conditions (e.g., binding partner availability, pH-dependence). This proposed intrinsic disorder across TNIP1 and within the AHD1-UBAN region is likely to impact TNIP1 function and interaction with its multiple partners.

Role of microRNA-15a-5p/TNFAIP3-interacting protein 2 axis in acute lung injury induced by traumatic hemorrhagic shock.

The present study aimed to investigate the role of microRNA (miR)-15a-5p in the pathogenesis of acute lung injury induced by traumatic hemorrhagic shock (THS), and to explore the underlying molecular mechanism. The expression level of miR-15a-5p was detected using reverse transcription-quantitative (RT-qPCR) and the association between miR-15a-5p and TNFAIP3-interacting protein 2 (TNIP2) was revealed using TargetScan and dual luciferase reporter assays. To investigate the effect of miR-15a-5p on THS-induced acute lung injury, a THS rat model was established. Lung capillary permeability and lung edema were then determined. Moreover, proinflammatory factors in the bronchoalveolar lavage fluid (BALF) and serum of the THS rat model were detected using ELISA. In addition, protein levels in the current study were measured via western blotting. It was revealed that miR-15a-5p was significantly upregulated in both patients with THS and samples from the THS rat model. TNIP2 represents a direct target of miR-15a-5p, and it was downregulated in both patients with THS and the THS rat model. Further analyses indicated that downregulation of miR-15a-5p significantly relieved acute lung injury induced by THS, evidenced by a decreased ratio of Evan's blue dye (EBD) in the BALF to EBD in plasma of THS rats, decreased lung permeability index and reduced lung wet/dry ratio. Inhibition of miR-15a-5p also decreased THS-induced upregulation of pro-inflammatory factors. Furthermore, the data revealed that THS-induced NF-κB activation in the lung tissues of rats was inhibited by miR-15a-5p knockdown. Moreover, it was demonstrated that all the effects of miR-15a-5p on THS rats were ablated following TNIP2 silencing. Taken together, the data of the current study indicate that miR-15a-5p downregulation serves a protective role in THS-induced acute lung injury via directly targeting TNIP2.

Enhanced Wound Healing- and Inflammasome-Associated Gene Expression in TNFAIP3-Interacting Protein 1- (TNIP1-) Deficient HaCaT Keratinocytes Parallels Reduced Reepithelialization.

TNIP1 protein is a widely expressed, cytoplasmic inhibitor of inflammatory signaling initiated by membrane receptors such as TLRs which recognize pathogen-associated and damage-associated molecular patterns (PAMPs and DAMPs). Keratinocyte TNIP1 deficiency sensitizes cells to PAMPs and DAMPs promoting hyperresponsive expression and secretion of cytokine markers (e.g., IL-8 and IL-6) relevant to cases of chronic inflammation, like psoriasis, where TNIP1 deficiency has been reported. Here, we examined the impact of TNIP1 deficiency on gene expression and cellular responses (migration and viability) relevant to acute inflammation as typically occurs in wound healing. Using siRNA-mediated TNIP1 expression knockdown in cultured HaCaT keratinocytes, we investigated TNIP1 deficiency effects on signaling downstream of TLR3 agonism with low-concentration poly (I:C), a representative PAMP/DAMP. The combination of TNIP1 knockdown and PAMP/DAMP signaling disrupted expression of specific keratinocyte differentiation markers (e.g., transglutaminase 1 and involucrin). These same conditions promoted synergistically increased expression of wound-associated markers (e.g., S100A8, TGFβ, and CCN2) suggesting potential benefit of increased inflammatory response from reduced TNIP1 protein. Unexpectedly, poly (I:C) challenge of TNIP1-deficient cells restricted reepithelialization and reduced cell viability. In these cells, there was not only increased expression for genes associated with inflammasome assembly (e.g., ASC, procaspase 1) but also for A20, a TNIP1 partner protein that represses cell-death signaling. Despite this possibly compensatory increase in A20 mRNA, there was a decrease in phospho-A20 protein, the form necessary for quenching inflammation. Hyperresponsiveness to poly (I:C) in TNIP1-deficient keratinocytes was in part mediated through p38 and JNK pathways. Taken together, we conclude that TNIP1 deficiency promotes enhanced expression of factors associated with promoting wound healing. However, the coupled, increased potential priming of the inflammasome and reduced compensatory activity of A20 has a net negative effect on overall cell recovery potential manifested by poor reepithelialization and viability. These findings suggest a previously unrecognized role for TNIP1 protein in limiting inflammation during successful progression through early wound healing stages.

Investigation of Potential Genetic Biomarkers and Molecular Mechanism of Ulcerative Colitis Utilizing Bioinformatics Analysis.

Objectives To reveal the molecular mechanisms of ulcerative colitis (UC) and provide potential biomarkers for UC gene therapy. Methods We downloaded the GSE87473 microarray dataset from the Gene Expression Omnibus (GEO) and identified the differentially expressed genes (DEGs) between UC samples and normal samples. Then, a module partition analysis was performed based on a weighted gene coexpression network analysis (WGCNA), followed by pathway and functional enrichment analyses. Furthermore, we investigated the hub genes. At last, data validation was performed to ensure the reliability of the hub genes. Results Between the UC group and normal group, 988 DEGs were investigated. The DEGs were clustered into 5 modules using WGCNA. These DEGs were mainly enriched in functions such as the immune response, the inflammatory response, and chemotaxis, and they were mainly enriched in KEGG pathways such as the cytokine-cytokine receptor interaction, chemokine signaling pathway, and complement and coagulation cascades. The hub genes, including dual oxidase maturation factor 2 (DUOXA2), serum amyloid A (SAA) 1 and SAA2, TNFAIP3-interacting protein 3 (TNIP3), C-X-C motif chemokine (CXCL1), solute carrier family 6 member 14 (SLC6A14), and complement decay-accelerating factor (CD antigen CD55), were revealed as potential tissue biomarkers for UC diagnosis or treatment. Conclusions This study provides supportive evidence that DUOXA2, A-SAA, TNIP3, CXCL1, SLC6A14, and CD55 might be used as potential biomarkers for tissue biopsy of UC, especially SLC6A14 and DUOXA2, which may be new targets for UC gene therapy. Moreover, the DUOX2/DUOXA2 and CXCL1/CXCR2 pathways might play an important role in the progression of UC through the chemokine signaling pathway and inflammatory response.

TNFAIP3 genetic polymorphisms reduce ankylosing spondylitis risk in Eastern Chinese Han population

This study was conducted to clarify the associations of tumor necrosis factor-α induced protein 3 (TNFAIP3) and TNFAIP3-interacting protein 1 (TNIP1) genetic polymorphisms with ankylosing spondylitis (AS) susceptibility. Five single nucleotide polymorphisms (SNPs) in TNFAIP3 gene and four in TNIP1 gene were genotyped in 667 AS patients and 667 matched healthy controls. Genotypes and haplotype analysis were conducted by using SPSS 23.0 and Haploview 4.2 software. The T allele and CT genotype in TNFAIP3 rs10499194 were significantly associated with a reduced AS risk (T allele vs. C allele, OR = 0.619, 95% CI = 0.430–0.889, P = 0.009; CT vs. CC, OR = 0.603, 95% CI = 0.416–0.875, P = 0.007). However, no association remained significant after Bonferroni correction. The rs13207033A- rs10499194T haplotype of TNFAIP3 conferred a protective effect on AS susceptibility. Stratification analyses suggested that rs10499194 polymorphism decreased the risk of AS in the male subgroup, subgroup aged ≥ 29, HLA-B27 positive subgroup as well as the subgroups of BASFI < 4 and BASDAI < 4 (all P < 0.05). Furthermore, the functional annotation suggested a potential function of rs10499194 mutation. Our results demonstrated that TNFAIP3 rs10499194 polymorphism may be associated with a reduced risk of AS.

Patrolling monocytes promote the pathogenesis of early lupus-like glomerulonephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with genetic and environmental contributions. Hallmarks of the disease are the appearance of immune complexes (IC) containing autoreactive Abs and TLR-activating nucleic acids, whose deposition in kidney glomeruli is suspected to promote tissue injury and glomerulonephritis (GN). Here, using a mouse model based on the human SLE susceptibility locus TNFAIP3-interacting protein 1 (TNIP1, also known as ABIN1), we investigated the pathogenesis of GN. We found that GN was driven by TLRs but, remarkably, proceeded independently of ICs. Rather, disease in 3 different mouse models and patients with SLE was characterized by glomerular accumulation of patrolling monocytes (PMos), a cell type with an emerging key function in vascular inflammation. Consistent with such function in GN, monocyte-specific deletion of ABIN1 promoted kidney disease, whereas selective elimination of PMos provided protection. In contrast to GN, PMo elimination did not protect from reduced survival or disease symptoms such as IC generation and splenomegaly, suggesting that GN and other inflammatory processes are governed by distinct pathogenic mechanisms. These data identify TLR-activated PMos as the principal component of an intravascular process that contributes to glomerular inflammation and kidney injury.

Pansteatitis Induced Differential Expression of Inflammatory and Apoptosis Genes in Adipose Tissue: A Glimpse into Pathophysiology of the Condition in the Nile Crocodile.

In the quest to understand the pathophysiology of pansteatitis in the Nile crocodile, a condition that was attributed to the recent crocodile die off at the Olifant river, Mpumalanga, the whole transcriptome of the Nile crocodile was sequenced and assembled using whole transcriptome shotgun sequencing data by Illumina RNAseq from RNA obtained from fat body and other adipose tissues.Total RNA, from abdominal fat body and other adipose tissue from normal farmed Nile crocodiles and samples collected from Nile crocodiles that had died of pansteatitis, were extracted and purified using Qiagen RNA mini prep (Qiagen, USA). RNA samples library were prepped using the Truseq stranded total RNA sample preparation and sequenced on the Illumina Hiseq 2500 with v4 SBS chemistry. Reads were assembled using Tophat (http://tophat.cbcb.umd.edu/) and aligned with reference transcriptome from Crocodylus porosus using Cufflinks (http://cufflinks.cbcb.umd.edu/) for downstream analysis while the differential gene expression analysis was done using Cuffdiff and RSEM (http://deweylab.github.io/RSEM/).A total of 13,329 genes were identified out which 1541 genes related to inflammatory response and apoptosis were identified. A total of 641 genes were up regulated in the pansteatitis samples as compared to normal adipose tissues using a fold change of 16.0. A total of 70 inflammatory genes were up regulated in the pansteatitis samples including, PDCD5 (programmed cell death 5), NFIL3 (nuclear factor, interleukin 3 regulated protein), HSP90B1 (heat shock protein 90kDa beta (Grp94), member 1), VCAM1 (vascular cell adhesion molecule 1), IL1R1 (interleukin 1 receptor, type I), TNIP1 (TNFAIP3 interacting protein 1), JAK1 (Janus kinase 1), TNFAIP2 (tumor necrosis factor, alpha‐induced protein 2) IL6ST (interleukin 6 signal transducer (gp130, oncostatin M receptor)) CFD (complement factor D (adipsin) and PPARG (peroxisome proliferator‐activated receptor gamma) among others. These genes are responsible for inflammation, apoptosis, regulation of Toll‐like receptors in inflammatory response, leucocyte migration and fibrosis in chronic inflammation.We present for the first time in the Nile crocodile, a comprehensive lists of inflammatory response genes that are expressed and up regulated in pansteatitis in the Nile crocodile.Support or Funding InformationPart of the study was funded by Tertiary Education Trust Fund (TETFund) AST and D, Nigeria and Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Variants at HLA-A, HLA-C, and HLA-DQB1 Confer Risk of Psoriasis Vulgaris in Japanese

Psoriasis vulgaris (PsV) is an autoimmune disease of skin and joints with heterogeneity in epidemiologic and genetic landscapes of global populations. We conducted an initial genome-wide association study and a replication study of PsV in the Japanese population (606 PsV cases and 2,052 controls). We identified significant associations of the single nucleotide polymorphisms with PsV risk at TNFAIP3-interacting protein 1and the major histocompatibility complex region (P= 3.7× 10-10 and 6.6× 10-15, respectively). By updating the HLA imputation reference panel of Japanese (n= 908) to expand HLA gene coverage, we fine-mapped the HLA variants associated with PsV risk. Although we confirmed the PsV risk of HLA-C*06:02 (odds ratio= 6.36, P=0.0015), its impact was relatively small compared with those in other populations due to rare allele frequency in Japanese (0.4% in controls). Alternatively, HLA-A*02:07, which corresponds to the cysteine residue at HLA-A amino acid position 99 (HLA-A Cys99), demonstrated the most significant association with PsV (odds ratio= 4.61, P= 1.2× 10-10). In addition to HLA-A*02:07 and HLA-C*06:02, stepwise conditional analysis identified an independent PsV risk of HLA-DQβ1 Asp57 (odds ratio= 2.19, P= 1.9× 10-6). Our PsV genome-wide association study in Japanese highlighted the genetic architecture of PsV, including the identification of HLA risk variants.

Association between genetic variants and esophageal cancer risk.

We investigated whether single nucleotide polymorphisms (SNPs) in the nuclear assembly factor 1 (NAF1) and TNFAIP3-interacting protein 1 (TNIP1) gene were associated with susceptibility to esophageal cancer in a Chinese Han population. Five SNPs were genotyped and their relationship with esophageal cancer risk was analyzed in a sample of 386 esophageal cancer patients and 495 unrelated healthy controls recruited from the First Affiliated Hospital of Xi’an Jiaotong University. Patients with the AG genotype of rs2320615 were at lower risk of developing esophageal cancer than those with the GG genotype (adjusted odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.46-0.90, P = 0.009). The rs2320615 SNP was found to be associated with a decreased the risk of esophageal cancer in the dominant model (adjusted OR = 0.70, 95% CI = 0.51-0.96, P = 0.026). These results provide the first evidence that the rs2320615 in NAF1 was associated with reduced risk of esophageal cancer. Further studies with larger samples are warranted to confirm our findings.

Upregulation of the C/EBP β LAP isoform could be due to decreased TNFAIP3/TNIP1 expression in the peripheral blood mononuclear cells of patients with systemic lupus erythematosus

Objectives: We aimed to examine CCAAT/enhancer-binding protein β (C/EBP β), TNF-alpha-induced protein 3 (TNFAIP3), and TNFAIP3-interacting protein 1 (TNIP1) expression in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients to assess their relationship in SLE pathogenesis.Methods: C/EBP β, TNIP1, and TNFAIP3 expression was assessed in PBMCs from 20 SLE patients and 20 controls by western blotting. The correlation between C/EBP β/TNFAIP3/TNIP1 expression and SLE disease activity was determined by Spearman’s rank. C/EBP β, TNIP1, and TNFAIP3 levels in THP-1 cells, THP-1 cells transfected with plasmids encoding TNFAIP3 shRNA, and THP-1 cells infected with lentiviral vectors encoding TNIP1 shRNA were assessed by western blotting.Results: C/EBP β LAP isoform expression was increased and LIP/TNFAIP3/TNIP1 expression was decreased in SLE patients. LAP expression was positively correlated with SLE disease activity; TNFAIP3 and TNIP1 expression was negatively correlated with SLE disease activity. LAP expression was increased in SLE patients with proteinuria and elevated anti-dsDNA antibody, as well as in THP-1 cells transfected with plasmids encoding TNFAIP3 shRNA and THP-1 cells infected with lentiviral vectors encoding TNIP1 shRNA.Conclusions: C/EBP β/TNFAIP3/TNIP1 is associated with SLE activity. The upregulated expression of C/EBP β LAP could be caused by reduced TNFAIP3/TNIP1 expression.

C/EBP β mRNA expression is upregulated and positively correlated with the expression of TNIP1/TNFAIP3 in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

CCAAT/enhancer-binding protein β (C/EBP β) has important roles in numerous signaling pathways. The expression of the majority of regulators and target gene products of C/EBP β, including tumor necrosis factor α-induced protein 3 (TNFAIP3) and TNFAIP3-interacting protein 1 (TNIP1), are upregulated in patients with systemic lupus erythematosus (SLE). The aim of the present study was to investigate whether C/EBP β expression is associated with SLE pathogenesis and correlates with TNIP1 and TNFAIP3 expression. Quantitative reverse transcription-polymerase chain reaction analysis was used to assess the expression of C/EBP β, TNIP1, and TNFAIP3 mRNA in peripheral blood mononuclear cells (PBMC) from 20 patients with SLE and 20 healthy controls. Spearman's rank test was used to determine the correlation between C/EBP β expression and SLE disease activity, and that between C/EBP β expression and TNIP1/TNFAIP3 expression in PBMCs from patients with SLE. C/EBP β mRNA expression was markedly increased in patients with SLE compared with healthy controls. The expression of C/EBP β was positively correlated with the SLE disease activity index and negatively correlated with the serum level of complement components C3 and C4. In addition, C/EBP β mRNA expression was increased in PBMCs from SLE patients that were positive for antinuclear, anti-Smith and anti-nRNP antibodies, compared with the antibody negative SLE patients. Furthermore, the mRNA expression levels of C/EBP β in patients with SLE was positively correlated with TNIP1 and TNFAIP3 expression. The results of the current study suggest that the increased expression of C/EBP β in PBMCs and the interaction between C/EBP β and TNIP1/TNFAIP3 may be involved in the pathogenesis of SLE.

The TNFR In Asterias rubens Sea Star: Genomic Studies

The sea star Asterias rubens includes TNFR, in its genome, when compared to mouse one: mouse isoform 2 of TNF AIP3-interacting protein 1, mouse TNF receptor-associated factor 2, mouse TNF receptor-associated factor 3, mouse TNF receptor-associated factor 4, mouse TNF receptor-associated factor 6. Many of these factors are bound to NF Kappa -B genes which have recently been isolated in the Asterias rubens genome. They play a role in the regulation of the sea star immune system.

TNFAIP3 and TNIP1 polymorphisms confer psoriasis risk in South Indian Tamils

Psoriasis is a chronic inflammatory skin disease with genetic and environmental factors having an important role in its aetiology. Several genome-wide association studies have reported the association of the genes of the TNFα signalling, tumour necrosis factor alpha-induced protein 3 (TNFAIP3), TNFAIP3-interacting protein 1 (TNIP1) with psoriasis in Western and Chinese populations. The aim of this study is to demonstrate whether the TNFAIP3 and TNIP1 genes contribute to the risk of psoriasis in he ethnically distinct South Indian population. 360 psoriatic subjects and 360 healthy controlswere recruited in this case control study. TNFAIP3 (rs610604) and TNIP1 (rs17728338) polymorphisms were typed by using TaqMan 5 allele discrimination assay. The results demonstrated that the SNPs rs610604 and rs17728338 of the TNFAIP3 and TNIP1 genes, respectively, were associated with psoriasis in our population at both allelic and genotypic levels. Thus, our results suggest that TNFAIP3 (rs610604 and TNIP1 (rs17728338) polymorphisms confer increased risk of psoriasis and may play a vital role in its pathogenesis in our ethnic South Indian Tamils.

Investigating the genetic association of HCP5, SPATA2, TNIP1, TNFAIP3 and COG6 with psoriasis in Chinese population.

Psoriasis is a chronic inflammatory skin disease occurred under the interaction of genetic and environmental factors. The genes HLA complex P5 (HCP5), spermatogenesis associated 2 (SPATA2), tumour necrosis factor alpha-induced protein 3 (TNFAIP3), TNFAIP3-interacting protein 1 (TNIP1) and the component of oligomeric Golgi complex 6 (COG6) were reported to be associated with psoriasis in western populations by genome-wide association studies. The aim of this study was to investigate whether the HCP5, TNIP1, TNFAIP3, SPATA2 and COG6 genes were genetic risk factors for psoriasis in Chinese population. One single nucleotide polymorphism (SNP) from each gene was evaluated using Chinese patients with psoriasis (n = 201) and controls (n = 300). The results demonstrated that SNPs rs2395029, rs17728338 and rs610604 from the HCP5, TNIP1 and TNFAIP3 genes, respectively, were associated with psoriasis in the studied population at both genotype level and allelic level (P < 0.05). Thus, the data suggested that HCP5, TNIP1 and TNFAIP3 may play a role in common pathogenic of psoriasis in Chinese and confer risk factors for psoriasis in various ethnic populations. These results provide potential makers for diagnosing, treating and preventing the psoriasis.