Disease relevance of IL29

• Antiproliferative activity was induced by IFNs in most cell lines, but only in one human glioblastoma cell line, LN319, was dose-dependent IL-29-growth inhibition demonstrable [1].
• Pegylated IL-29 also produced a significant reduction in human hepatitis B and hepatitis C viral load in vitro and reduced the cytopathic effect caused by the fully replicating flavivirus, West Nile virus [2].
• Influenza A virus also enhanced the binding of NF-kappaB to the respective NF-kappaB elements of the promoters of IFN-beta and IL-29 genes [3].
• AIM: To construct the recombinant vectors carrying interleukin (IL)-28A, IL-28B and IL-29 cDNAs and express them in human A549 cells, and analyze their antiviral activity in vesicular stomatitis virus (VSV)-infected human immortalized amnion epithelial cell line (WISH cells) [4].
• Murine B16 melanoma and Colon26 cancer cells were transduced with mouse IFN-lambda to determine whether IFN-lambda possesses antitumor activity [5].

High impact information on IL29

• Three closely positioned genes on human chromosome 19 encode distinct but paralogous proteins, which we designate interferon-lambda1 (IFN-lambda1), IFN-lambda2 and IFN-lambda3 (tentatively designated as IL-29, IL-28A and IL-28B, respectively, by HUGO) [6].
• Similar observation were obtained in human TLR8-expressing monocyte-derived DC (moDC) using neutralizing anti-IFNAR2 antibodies, although results also pointed to a possible involvement of IFN-lambda1 (also known as IL-29) [7].
• Interferon-lambda-treated dendritic cells specifically induce proliferation of FOXP3-expressing suppressor T cells [8].
• In this work, we show that DCs acquire IFN-lambda responsiveness through the expression of the specific IFN-lambda receptor chain during their differentiation from monocytes [8].
• In conclusion, IL-29 and IFN-alpha stimulate identical antiviral responses despite their utilization of different receptors [2].

Biological context of IL29

• Both IL-28A and IL-29 significantly decrease cell proliferation but have no effect on Fas-induced apoptosis [9].
• Additionally, we showed IL-28A and IL-29 induced reporter genes--protein MxA promoter linked to luciferase, or interferon stimulated response element (ISRE) linked to secreted alkaline phosphatase (SEAP)--more weakly than IFN [1].
• Here, we show that activation of this receptor by IFN-lambda 1 can also inhibit cell proliferation and induce STAT4 phosphorylation, further extending functional similarities with type I IFNs [10].
• On the other hand, IL-28 and IL-29 are considered to be critical for mounting an efficient antiviral response and IL-32 and IL-33, which are yet to be fully characterized, are emerging as important components of the inflammatory response in allergy and autoimmunity [11].
• CONCLUSION: IL-28 and IL-29 cDNAs were successfully cloned and expressed in eukaryotic cells via transfection with pcDNA3.1/V5-His-TOPO-IL-28/IL-29 [4].

Anatomical context of IL29

• First, we show that hepatic cell lines express the IFN-lambda receptor complex consisting of IFN-lambdaR1 (IL-28R1) and IL-10R2 [12].
• Here, we demonstrate that intestinal epithelial cell (IEC) lines as well as murine and human colonic tissue express the IFN-lambda receptor subunits IL-28R and IL-10R2 [9].
• IFN-lambda expression in tumor cell lines markedly inhibited s.c. and metastatic tumor formation in vivo compared with mock transfections (p < 0.05) [5].
• Moreover, IFN-lambda expression induced lymphocytic infiltrates, and an Ab-mediated immune cell depletion assay showed that NK cells were critical to IFN-lambda-mediated tumor growth inhibition [5].
• The discrepancy between the observed antiviral activity in vitro and in vivo may suggest that IFN-lambda exerts a significant portion of its antiviral activity in vivo via stimulation of the immune system rather than through induction of the antiviral state [13].

Associations of IL29 with chemical compounds

• Role of the interleukin (IL)-28 receptor tyrosine residues for antiviral and antiproliferative activity of IL-29/interferon-lambda 1: similarities with type I interferon signaling [10].
• Liposome-mediated IL-28 and IL-29 expression in A549 cells and anti-viral effect of IL-28 and IL-29 on WISH cells [4].
• It involved of cloning IL-29 gene into the pET-44 Ek/LIC vector, which allowed expression of IL-29 with a fusion tag consisting of the NusA protein, polyhistidine and S peptide (Nus-His-S-tag), and introducing a thrombin recognition site between the fusion tag and IL-29 [14].

Regulatory relationships of IL29

• Finally, pretreatment with IFN-lambda enhanced the levels of IFN-gamma in serum after HSV-2 infection [13].

Other interactions of IL29

• The interferon lambda family (IFN-lambda1/2/3) is a newly described group of cytokines that are related to both the type-1 interferons and IL-10 family members [15].
• Treatment of THP-1 cells, a human monocytic cell line, with recombinant human interferon-lambda reduced the levels of thymosin-beta 4 mRNA [16].
• The expressed fusion protein was purified by S-protein agarose affinity chromatography, and the fusion tag was removed from recombinant IL-29 by cleavage with thrombin [14].

Analytical, diagnostic and therapeutic context of IL29

• The cDNAs encoding human IL-28A, IL-28B, and IL-29 were amplified by reverse-transcription polymerase chain reaction (RT-PCR) and inserted into pcDNA3.1/V5-His-TOPO vectors [4].
• In mixed lymphocyte reaction (MLR) cultures, IFN-lambda-treated DCs specifically induced IL-2-dependent proliferation of a CD4(+)CD25(+)Foxp3(+) T-cell subset with contact-dependent suppressive activity on T-cell proliferation initiated by fully mature DCs [8].
• The purified IL-29 appeared a single band on SDS-PAGE, and the yield of IL-29 was 60 mg from 1 l of bacterial culture [14].

References