Polymorphisms in the Interferon Regulatory Factor-1 Promoter Are Not Associated with Psoriasis and Do Not Influence IFN-<i>α</i>-Induced Th1 Polarization

Fits, Leslie van der; Kant, Marius; Wel, Leontine I van der; Prens, Errol P.

doi:10.1089/jir.2007.0013

Cited by 3 publications

(2 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CXCL2 that has function in immune response is over-expressed in osteoarthritis fibroblasts rather than rheumatoid fibroblasts [47], up-regulated in psoriatic epidermis [48], and also in epithelial tissue [49]. IL10 is expressed in PBMCs of psoriasis [50], RA [51] and IBD patients [52]. The expression of NAMPT which is a pre-B cell-enhancing factor is increased in colonic biopsy specimens of IBD patients compared to healthy controls [53], it is also up-regulated in plasma and synovial fluid of RA patients [54]; and in PBMC of psoriasis in the diseased stage [10].…”

Section: Discussionmentioning

confidence: 99%

Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets

et al. 2010

View full text Add to dashboard Cite

BackgroundChronic inflammatory diseases including inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), psoriasis and rheumatoid arthritis (RA) afflict millions of people worldwide, but their pathogenesis is still not well understood.It is also not well known if distinct changes in gene expression characterize these diseases and if these patterns can discriminate between diseased and control patients and/or stratify the disease. The main focus of our work was the identification of novel markers that overlap among the 3 diseases or discriminate them from each other.MethodsDiseased (n = 13, n = 15 and n = 12 in IBD, psoriasis and RA respectively) and healthy patients (n = 18) were recruited based on strict inclusion and exclusion criteria; peripheral blood samples were collected by clinicians (30 ml) in Venous Blood Vacuum Collection Tubes containing EDTA and peripheral blood mononuclear cells were separated by Ficoll gradient centrifugation. RNA was extracted using Trizol reagent. Gene expression data was obtained using TaqMan Low Density Array (TLDA) containing 96 genes that were selected by an algorithm and the statistical analyses were performed in Prism by using non-parametric Mann-Whitney U test (P-values < 0.05).ResultsHere we show that using a panel of 96 disease associated genes and measuring mRNA expression levels in peripheral blood derived mononuclear cells; we could identify disease-specific gene panels that separate each disease from healthy controls. In addition, a panel of five genes such as ADM, AQP9, CXCL2, IL10 and NAMPT discriminates between all samples from patients with chronic inflammation and healthy controls. We also found genes that stratify the diseases and separate different subtypes or different states of prognosis in each condition.ConclusionsThese findings and the identification of five universal markers of chronic inflammation suggest that these diseases have a common background in pathomechanism, but still can be separated by peripheral blood gene expression. Importantly, the identified genes can be associated with overlapping biological processes including changed inflammatory response. Gene panels based on such markers can play a major role in the development of personalized medicine, in monitoring disease progression and can lead to the identification of new potential drug targets in chronic inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets

et al. 2010

View full text Add to dashboard Cite

show abstract

“…IRF1 is one of the transcription factors regulating type I IFN responses. Although SNPs of the IRF1 promoter may be related to the T-helper type 1 (Th1) response in chronic hepatitis C infection 38 , studies have found no association between SNPs of the IRF1 promoter and the pathogenesis of psoriasis 39 . IRF1 has been observed throughout the epidermis in both normal skin and psoriatic lesions 40 , but one study reported that IRF1 expression is lower in psoriatic lesions than in non-lesions of patients with psoriasis or normal skin.…”

Section: Irfs and Psoriasismentioning

confidence: 99%

Role of interferon regulatory factor-mediated signaling in psoriasis

2021

View full text Add to dashboard Cite

Psoriasis is a chronic inflammatory disease that involves both the innate and adaptive immune systems. Type I interferons (IFNs), the production of which is partially regulated by toll-like receptors (TLRs), play an important role in the pathogenesis of psoriasis, especially psoriasis caused by skin trauma, known as the Koebner phenomenon. IFN regulatory factors (IRFs) function in both innate and adaptive immune responses, and their effect is associated with the regulation of type I IFNs. In this review, we focus on recent advances in understanding the expression of TLRs, IRFs, and type I IFNs in psoriasis. We also highlight the interplay among TLRs, IRFs, and type I IFNs.

show abstract

Exacerbated Imiquimod-Induced Psoriasis-Like Skin Inflammation in IRF5-Deficient Mice

Nakao

Miyagaki

Sugaya

et al. 2020

IJMS

View full text Add to dashboard Cite

Interferon regulatory factors (IRFs) play diverse roles in the regulation of the innate and adaptive immune responses in various diseases. In psoriasis, IRF2 is known to be involved in pathogenesis, while studies on other IRFs are limited. In this study, we investigated the role of IRF5 in psoriasis using imiquimod-induced psoriasis-like dermatitis. Although IRF5 is known to play a critical role in the induction of proinflammatory cytokines by immune cells, such as dendritic cells (DCs), macrophages, and monocytes, IRF5 deficiency unexpectedly exacerbated psoriasiform skin inflammation. The interferon-α and tumor necrosis factor-α mRNA expression levels were decreased, while levels of Th17 cytokines including IL-17, IL-22, and IL-23 were increased in IRF5-deficient mice. Furthermore, IL-23 expression in DCs from IRF5-deficient mice was upregulated both in steady state and after toll-like receptor 7/8 agonist stimulation. Importantly, the expression of IRF4, which is also important for the IL-23 production in DCs, was augmented in DCs from IRF5-deficient mice. Taken together, our results suggest that IRF5 deficiency induces the upregulation of IRF4 in DCs followed by augmented IL-23 production, resulting in the amplification of Th17 responses and the exacerbation of imiquimod-induced psoriasis-like skin inflammation. The regulation of IRF4 or IRF5 expression may be a novel therapeutic approach to psoriasis.

show abstract

Polymorphisms in the Interferon Regulatory Factor-1 Promoter Are Not Associated with Psoriasis and Do Not Influence IFN-α-Induced Th1 Polarization

Cited by 3 publications

References 30 publications

Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets

Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets

Role of interferon regulatory factor-mediated signaling in psoriasis

Exacerbated Imiquimod-Induced Psoriasis-Like Skin Inflammation in IRF5-Deficient Mice

Contact Info

Product

Resources

About