Human interleukin-1 beta gene

Bensi, G; Raugei, Giovanni; Palla, Emanuela; Carinci, Valeria; Buonamassa, Daniela Tornese; Melli, Marialuisa

doi:10.1016/0378-1119(87)90398-2

Cited by 84 publications

(37 citation statements)

References 19 publications

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“…Similar to the human IL-1␤ gene (48), the carp IL-1␤ gene has seven exons and six introns (44), whereas S. canicula, chicken, trout IL-1␤1 (34), and trout IL-1␤2 (8) have six exons and five introns. In S. canicula and chicken it is clear that the first intron is missing in the 5Ј UTR, whereas in trout the equivalent of an exon and an intron appear to be missing at the 5Ј end (34).…”

Section: Discussionmentioning

confidence: 99%

The First Cytokine Sequence Within Cartilaginous Fish: IL-1β in the Small Spotted Catshark (Scyliorhinus canicula)

Bird

Wang

Zou

et al. 2002

The Journal of Immunology

106

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Cartilaginous fish are considered the most primitive living jawed vertebrates with a complex immune system typical of all jawed vertebrates. Cytokine homologs are found within jawless and bony fish, although no cytokine or cytokine receptor genes have been sequenced in cartilaginous fish. In this study the complete coding sequence of the small spotted catshark (Scyliorhinus canicula) IL-1β gene is presented that contains a short 5′ untranslated region (54 bp), a 903-bp open reading frame, a 379-bp 3′ untranslated region, a polyadenylation signal, and eight mRNA instability motifs. The predicted translation (301 amino acids) has highest identity to trout IL-1β (31.7%), with greatest homology within the putative 12 β-sheets. The IL-1 family signature is also present, but there is no apparent signal peptide. As with other nonmammalian IL-1β sequences, the IL-1-converting enzyme cut site is absent. Expression of the IL-1β transcript is detectable by RT-PCR in the spleen and testes, induced in vivo with LPS. Furthermore, a 7-fold increase of transcript levels in splenocytes incubated for 5 h with LPS was seen. The genomic organization comprises six exons and five introns with highest homology seen in exons encoding the largest amount of secondary structure per amino acid. Southern blot analysis suggests at least two copies of the IL-1β gene or genes related to the 3′ end of the IL-1β sequence are present in the catshark. The cloning of IL-1β in S. canicula, the first cytokine sequenced within cartilaginous fish, verifies previous bioactivity evidence for the presence of inflammatory cytokines.

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Section: Discussionmentioning

confidence: 99%

The First Cytokine Sequence Within Cartilaginous Fish: IL-1β in the Small Spotted Catshark (Scyliorhinus canicula)

Bird

Wang

Zou

et al. 2002

The Journal of Immunology

106

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“…The IL-1, gene spans a region of 7.5 kb with a coding region divided into seven exons (4,7,31 (20). Pro-IL-10 is an inactive 31-kDa precursor that is cleaved by IL-10-converting enzyme between Asp-116 and Ala-117, releasing the 153 COOH-terminal amino acids that constitute the mature cytokine (4,9,31).…”

Section: Discussionmentioning

confidence: 99%

Regulation of the interleukin-1 beta (IL-1 beta) gene by mycobacterial components and lipopolysaccharide is mediated by two nuclear factor-IL6 motifs.

Zhang¹,

Rom²

1993

Mol. Cell. Biol.

118

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The cytokines interleukin-113 and tumor necrosis factor alpha (TNF-a) (-90/-82 and -40/-32) with high homology to the nuclear factor-IL6 (NF-IL6) binding site. Site-directed mutagenesis demonstrated that the two NF-IL-6 motifs could be independently activated by LAM, LPS, or TNF-a and that they acted in an orientation-independent manner. DNA mobility shift assay revealed specific binding of nuclear protein(s) from LAM-, LPS-, or TNF-a-stimulated THP-1 cells to the NF-EL6 motifs. We conclude that the two NF-IL6 sites mediate induction of IL-11" in response to the stimuli LAM, LPS, and TNF-cx.Tuberculosis is characterized by granuloma formation with caseation necrosis and systemic symptoms of weight loss, fever, and night sweats (8). Animal models demonstrate cytokines in the granulomas, and in vitro experiments with mononuclear phagocytes have established that Mycobacterum tuberculosis stimulates the release of cytokines (5,6,25,33,40,41). Interleukin-lp (IL-1,B) and tumor necrosis factor alpha (TNF-a) are the two major inflammatory mediators released in vitro by mycobacteria (5, 13). IL-l1 is chemotactic for lymphocytes and can activate CD4+ helperinducer T lymphocytes, causing them to proliferate and release gamma interferon (IFN--y) (22). IL-1 and IFN--y stimulate macrophages to release TNF-a, which can also stimulate the release of 35). Studies of recombinant IL-1 impregnated in ethyl vinyl disks revealed that IL-1 could directly induce a granulomatous response in juxtaposition to the implanted disks (17, 27). Pulmonary granulomas induced in mice by the intratracheal injection of antigencoated beads were excised, and aqueous extracts of the granulomata contained high levels of IL-1 (26). Studies by Kunkel and colleagues demonstrated that IL-lp is the dominant cytokine in early schistosomal granuloma development, followed temporally by TNF-a (27). Thus, IL-1 may be more important to the early cellular recruitment of inflammatory cells and their activation, while TNF-a may contribute to the continued organization of the mature granulomatous lesion. Activation of the IL-1i gene is achieved by a number of stimuli, including lipopolysaccharide (LPS) from gram-negative bacteria, phorbol esters, silica, and other bacterial products (18,30,36,43).Although mycobacteria do not possess LPS, the cell wall of M. tuberculosis contains a complex lipid glycoprotein * Corresponding author. called lipoarabinomannan (LAM) which shares many physicochemical properties with LPS (5, 12). The cell wall backbone of LAM is complemented by phenolic glycolipids, mycolic acids, arabinogalactan, peptidoglycan, and mannophosphoinositides. However, the most antigenic and consequently biologically active component is LAM (10). In addition to stimulating cytokine release, LAM inhibits IFN-y activation of macrophages and protein-antigen processing by antigen-presenting cells and can suppress T-lymphocyte proliferation in vitro in response to mitogens and specific antigens (5,32,39). Barnes and colleagues demonstrated that the phosphoinosi...

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“…Evidence that the activity of IL-1 might be (35)(36)(37)(38), and the IL-lra gene is based on the sequences of the cloned genes for human, mouse, and rat IL-lra (Figs. 1 and 2a).…”

Section: Resultsmentioning

confidence: 99%

Interleukin 1 receptor antagonist is a member of the interleukin 1 gene family: evolution of a cytokine control mechanism.

Eisenberg¹,

Brewer²,

Verderber³

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

207

102

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Interleukin 1 receptor antagonist (IL-lra) is a protein that binds to the IL-1 receptor and blocks the binding of both IL-la and -.8 without inducing a signal of its own.Human IL-lra has some sequence identity to human IL-1(3, but the evolutionary relationship between these proteins has been unclear. We show that the genes for human, mouse, and rat IL-lra are similar to the genes for IL-la and IL-1(3 in intron-exon organization, indicating that gene duplication events were important in the creation of this gene family. Furthermore, an analysis of sequence comparisons and mutation rates for IL-la, IL-1pj, and IL-lra suggests that the duplication giving rise to the IL-lra gene was an early event in the evolution of the gene family. Comparisons between the mature sequences for IL-lra, IL-la, and IL-1(3 suggest that IL-lra has a P-stranded structure like to IL-la and IL-1iB, consistent with the three proteins being related. The N-terminal sequences of IL-lra appear to be derived from a region of the genome different than those of IL-la and IL-1p3, thus explaining their different modes of biosynthesis and suggesting an explanation for their different biological activities.Interleukin 1 (IL-1) is believed to be important in mediating inflammatory and immune responses (1, 2). IL-1 proteins have been cloned from several species, and in each case two proteins have been identified (3). These two proteins, IL-la and IL-1,3, have the same biological activities and bind to the same cell-surface receptors (4-6).Inhibitors of IL-1 have been reported in the literature over the past several years (7,8). We recently reported the isolation, cloning, and characterization of a cDNA for a protein from human monocytes, IL-lra, that acts as a receptor antagonist on the 80-kDa IL-1 receptor (9, 10). Subsequently, Carter et al. (11) isolated and cloned an IL-1 inhibitor from the human monocyte-like cell line U937 and showed on the basis of its sequence that this molecule is IL-lra. IL-lra appears to be related to the IL-1 family based on its homology and similar hydropathy profile to IL-1,, but unlike the IL-1 proteins, IL-lra has a classical secretory leader peptide and is glycosylated at a consensus N-linked glycosylation site (9, 10).To determine whether IL-1 and IL-lra evolved from a common precursor or whether their similarities are the result of convergent evolution of a structure that can bind to the IL-1 receptor, we isolated genomic clones for IL-lra from human, mouse, and rat and compared their coding sequences with those of IL-la and IL-1,8 from the same and other species.* Our findings support the view that these three proteins have a common ancestor and that the gene leading to IL-lra diverged early in the evolutionary history of the IL-1 family. The results also argue for an important role ofthe sequence around the N terminus of IL-1ra in the unique properties of this protein.

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Human interleukin-1 beta gene

Cited by 84 publications

References 19 publications

The First Cytokine Sequence Within Cartilaginous Fish: IL-1β in the Small Spotted Catshark (Scyliorhinus canicula)

The First Cytokine Sequence Within Cartilaginous Fish: IL-1β in the Small Spotted Catshark (Scyliorhinus canicula)

Regulation of the interleukin-1 beta (IL-1 beta) gene by mycobacterial components and lipopolysaccharide is mediated by two nuclear factor-IL6 motifs.

Interleukin 1 receptor antagonist is a member of the interleukin 1 gene family: evolution of a cytokine control mechanism.

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