Human IL-29 _Interleukin-29 Protein Vector: HEK293
- Known as:
- Human Interleukin-29 _Interleukin-29 Protein Vector: HEK293
- Catalog number:
- 10219-H01H
- Product Quantity:
- 10μg
- Category:
- -
- Supplier:
- Provo
- Gene target:
- Human IL-29 _Interleukin-29 Protein Vector: HEK293
Related genes to: Human IL-29 _Interleukin-29 Protein Vector: HEK293
- Gene:
- IFNL1 NIH gene
- Name:
- interferon lambda 1
- Previous symbol:
- IL29
- Synonyms:
- IL-29
- Chromosome:
- 19q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2002-12-02
- Date modifiied:
- 2016-10-11
Related products to: Human IL-29 _Interleukin-29 Protein Vector: HEK293
Related articles to: Human IL-29 _Interleukin-29 Protein Vector: HEK293
- In this study, we used a three-dimensional airway "organ tissue equivalent" (OTE) model at an air-liquid interface (ALI) to mimic human airways. We investigated the effects of three viruses (Influenza A virus (IAV), Human metapneumovirus (MPV), and Parainfluenza virus type 3 (PIV3) on this model, incorporating various control conditions for data integrity. Our primary objective was to assess gene expression using the NanoString platform in OTE models infected with these viruses at 24- and 72-hour intervals, focusing on 773 specific genes. To enhance the comprehensiveness of our analysis, we introduced a novel algorithm, namely MAS (Magnitude-Altitude Score). This innovative approach uniquely combines biological significance, as indicated by fold changes in gene expression, with statistical rigor, as represented by adjusted p-values. By incorporating both dimensions, MAS ensures that the genes identified as differentially expressed are not mere statistical artifacts but hold genuine biological relevance, providing a more holistic understanding of the airway tissue response to viral infections. Our results unveiled distinct patterns of gene expression in response to viral infections. At 24 hours post-IAV infection, a robust interferon-stimulated gene (ISG) response was evident, marked by the upregulation of key genes including IFIT2, RSAD2, IFIT3, IFNL1, IFIT1, IFNB1, ISG15, OAS2, OASL, and MX1, collectively highlighting a formidable antiviral defense. MPV infection at the same time point displayed a dual innate and adaptive immune response, with highly expressed ISGs, immune cell recruitment signaled by CXCL10, and early adaptive immune engagement indicated by TXK and CD79A. In contrast, PIV3 infection at 24 hours triggered a transcriptional response dominated by ISGs, active immune cell recruitment through CXCL10, and inflammation modulation through OSM. The picture evolved at 72 hours post-infection. For IAV, ISGs and immune responses persisted, suggesting a sustained impact. MPV infection at this time point showed a shift towards IL17A and genes related to cellular signaling and immune responses, indicating adaptation to the viral challenge over time. In the case of PIV3, the transcriptional response remained interferon-centric, indicating a mature antiviral state. Our analysis underscored the pivotal role of ISGs across all infections and time points, emphasizing their universal significance in antiviral defense. Temporal shifts in gene expression indicative of adaptation and fine-tuning of the immune response. Additionally, the identification of shared and unique genes unveiled host-specific responses to specific pathogens. IAV exerted a sustained impact on genes from the initial 24 hours, while PIV3 displayed a delayed yet substantial genomic response, suggestive of a gradual and nuanced strategy. - Source: PubMed
Publication date: 2024/11/26
Rezapour MostafaWalker Stephen JOrnelles David ANiazi Muhammad Khalid KhanMcNutt Patrick MAtala AnthonyGurcan Metin Nafi - Janus kinases (JAKs) bind to class I and II cytokine receptors, activating signaling and regulating gene transcription through signal transducer and activator of transcription (STAT) proteins. Type I interferons (IFNs) require the JAK members TYK2 and JAK1, which bind to the receptor subunits IFNAR1 and IFNAR2, respectively. We investigated the role of JAKs in regulating IFNAR signaling activity. Synthetic IFNARs in which the extracellular domains of IFNAR1 and IFNAR2 are replaced with nanobodies had near-native type I IFN signaling, whereas the homomeric variant of IFNAR2 initiated much weaker signaling, despite harboring docking sites for JAKs and STATs. Cells with JAK1 and TYK2 knockout (KO) showed residual signaling, suggesting partial complementation by the remaining JAKs, particularly when they were overexpressed. Live-cell micropatterning experiments confirmed the promiscuous binding of JAK1, JAK2, and TYK2 to IFNAR1 and IFNAR2, and their recruitment correlated with their relative cellular abundances. However, each JAK had a different efficacy in inducing cross-phosphorylation and downstream signaling. JAK binding was also promiscuous for other cytokine receptors, including IFN-L1, IL-10Rβ, TPOR, and GHR, but not for EPOR, which activated different downstream signaling pathways. These findings suggest that competitive binding of JAKs to cytokine receptors together with the varying absolute and relative abundances of the JAKs in different cell types can account for the cell type-dependent signaling pleiotropy of cytokine receptors. - Source: PubMed
Publication date: 2024/11/19
Zoler EyalMeyer ThomasBellón Junel SotolongoMönnig MiaSun BoyuePiehler JacobSchreiber Gideon - Human interferon (IFN) lambda (IFNL, IFN-L or IFN-λ) locus has several functional genetic variants but their role in regulating in vivo gene expression, and whether they associate with antiviral states in healthy individuals, is not clear. In this study, we recruited ∼550 healthy individuals belonging to both sexes, genotyped them for several IFNL genetic variants and measured, by qPCR, the expression of IFNL2/3, IFNL4 and four IFN-stimulated genes (ISGs) (MX1, OAS1, ISG15 and RSAD2) from their peripheral blood mononuclear cells (PBMC) both before and after stimulation with a viral mimic, poly I: C. We also measured secreted levels of several cytokines including IFN-λ1 and IFN-λ3 in poly I:C stimulated PBMCs. We found that males secrete higher levels of IFN-λs than females. The IFNL3/4 genetic variants significantly associated with secreted levels of both IFN-λ1 and IFN-λ3 in opposite directions, only in males. While the IFNL3/4 variants significantly associated with ISG expression either in basal or poly I:C induced or in both states, the direction of effect was opposite for the two sexes, suggesting that sex was a strong effect modifier. We did not see this trend in the association of ISG expression with the IFNL1 polymorphism, rs7247086, whose association with ISG expression and secreted IFN-λ3 levels was seen in females but not in males. Further, expression of several genes was associated with the IFN-λ4 activity-modifying variant rs117648444. However, we neither saw any strong correlation between levels of IFN-λ1/3 and ISG expression, nor did we see any strong evidence of IFNL4 expression that could be responsible for the association between ISG expression and IFNL genetic variants. These results suggest that there are complex interactions involving gender, IFN-λs, IFN-λ genetic variants and antiviral states in humans. - Source: PubMed
Publication date: 2024/10/17
Roy Debarati GuhaDe ManjarikaBharatiya SeemaKhedekar Dhanashree ADatta KallolBhattacharjee SamsiddhiChinnaswamy Sreedhar - Despite bevacizumab being the first biological agent approved for the treatment of metastatic colorectal cancer (mCRC), there is not any established DNA biomarker to improve its efficacy and personalize the treatment. - Source: PubMed
Stránská JBartáková KRožánková ZKotková LVrbková JTrojanec RFlodr PJurtíková HLíznerová BDrábek J - The recent pandemic was caused by the emergence of a new human pathogen, SARS-CoV-2. While the rapid development of many vaccines provided an end to the immediate crisis, there remains an urgent need to understand more about this new virus and what constitutes a beneficial immune response in terms of successful resolution of infection. Indeed, this is key for development of vaccines that provide long lasting protective immunity. The interferon lambda (IFNL) family of cytokines are produced early in response to infection and are generally considered anti-viral and beneficial. However, data regarding production of IFNL cytokines in coronavirus disease 2019 (COVID-19) patients is highly variable, and generally from underpowered studies. In this study, we measured all three IFNL1, IFNL2, and IFNL3 cytokines in plasma from a well characterized, large COVID-19 cohort (n = 399) that included good representation from patients with a more indolent disease progression, and hence a beneficial immune response. While all three cytokines were produced, they differed in both the frequency of expression in patients, and the levels produced. IFNL3 was produced in almost all patients but neither protein level nor IFNL3/IFNL4 single nucleotide polymorphisms were associated with clinical outcome. In contrast, both IFNL1 and IFNL2 levels were significantly lower, or absent, in plasma of patients that had a more severe disease outcome. These data are consistent with the concept that early IFNL1 and IFNL2 cytokine production is protective against SARS-CoV-2 infection. - Source: PubMed
Woods ElenaMena AdrianaSierpinska SophieCarr EmilySttar Bioresource Hagan RichardCrowley JohnBergin ColmClark DavidBrophy CarolineMacallan DerekGardiner Clair M