Genomic Organization of the Interleukin-1 Locus

Taylor, Scott L.; Renshaw, Blair R.; Garka, Kirsten E.; Smith, Dirk E.; Sims, John E.

doi:10.1006/geno.2002.6752

Cited by 130 publications

(124 citation statements)

References 23 publications

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“…Different from most IL-1 family members, IL-37 has emerged as an anti-inflammatory cytokine. At the present time, a mouse homolog has not been identified; however, five splice variants of human IL-37 have been described (IL-37a-f) (10)(11)(12)(13). The IL-37a isoform has a unique N terminus encoded by exon 3 (11), whereas the short isoforms IL-37c, IL-37d, and IL-37e lack exon 4, exon 2, or both exons, respectively.…”

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confidence: 95%

“…At the present time, a mouse homolog has not been identified; however, five splice variants of human IL-37 have been described (IL-37a-f) (10)(11)(12)(13). The IL-37a isoform has a unique N terminus encoded by exon 3 (11), whereas the short isoforms IL-37c, IL-37d, and IL-37e lack exon 4, exon 2, or both exons, respectively. None of the N-terminal sequences encoded by exon 1 contain a prodomain, and it remains unclear whether IL-37 is processed by caspase-1 to an active form (10,14).…”

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confidence: 95%

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Interleukin 37 expression protects mice from colitis

McNamee

Masterson

Jedlicka

et al. 2011

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

294

280

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IL-37, a newly described member of the IL-1 family, functions as a fundamental inhibitor of innate inflammation and immunity. In the present study, we examined a role for IL-37 during experimental colitis. A transgenic mouse strain was generated to express human IL-37 (hIL-37tg), and these mice were subjected to dextran sulfate sodium (DSS)-induced colitis. Despite the presence of a CMV promoter to drive expression of IL-37, mRNA transcripts were not present in colons at the resting state. Expression was observed only upon disruption of the epithelial barrier, with a six-to sevenfold increase (P = 0.02) on days 3 and 5 after continuous exposure to DSS. During the development of colitis, clinical disease scores were reduced by 50% (P < 0.001), and histological indices of colitis were one-third less in hIL-37tg mice compared with WT counterparts (P < 0.001). Reduced inflammation was associated with decreased leukocyte recruitment into the colonic lamina propria. In addition, release of IL-1β and TNFα from ex vivo colonic explant tissue was decreased 5-and 13-fold, respectively, compared with WT (P £ 0.005), whereas IL-10 was increased sixfold (P < 0.001). However, IL-10 was not required for the anti-inflammatory effects of IL-37 because IL-10-receptor antibody blockade did not reverse IL-37-mediated protection. Mechanistically, IL-37 originating from hematopoietic cells was sufficient to exert anti-inflammatory effects because WT mice reconstituted with hIL-37tg bone marrow were protected from colitis. Thus, IL-37 emerges as key modulator of intestinal inflammation.cytokine | intestine | inflammatory bowel disease

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confidence: 95%

mentioning

confidence: 95%

Interleukin 37 expression protects mice from colitis

McNamee

Masterson

Jedlicka

et al. 2011

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

294

280

View full text Add to dashboard Cite

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“…Recently, six new IL-1 family genes have been mapped between IL1B and IL1RN: IL1F7, IL1F9, IL1F6, IL1F8, IL1F5 and IL1F10. 21,22 These genes share the same common ancestor as IL-1 and IL-18, with regions of amino acid and genetic homology, but their function is currently uncharacterised. The IL1A, IL1B and IL1RN genes have been extensively examined for polymorphic nucleotide residues: the literature on these polymorphisms, their effect on gene expression, and their influence on human diseases has been reviewed.…”

Section: Introductionmentioning

confidence: 99%

Extended haplotypes and linkage disequilibrium in the IL1R1–IL1A–IL1B–IL1RN gene cluster: association with knee osteoarthritis

et al. 2004

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The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P ¼ 0.00043; P c ¼ 0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P ¼ 0.0036; P c ¼ 0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P ¼ 0.02), and the protective IL1B-IL1RN haplotype conferred a fivefold reduced risk of OA (P ¼ 0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA.

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“…These proteins share a common ␤-barrel pattern consisting of 12 ␤-strands and significant amino acid homology with the IL-1 receptor antagonist (IL-1Ra), IL-1␤, and IL-18. The new members of the IL-1 family are derived from a common ancestor, as are IL-1 and IL-18 (11,12). Except for IL-18, each maps to the same region on human chromosome 2 (4,(11)(12)(13).…”

mentioning

confidence: 99%

“…The new members of the IL-1 family are derived from a common ancestor, as are IL-1 and IL-18 (11,12). Except for IL-18, each maps to the same region on human chromosome 2 (4,(11)(12)(13). On the basis of their structure these IL-1 family members potentially can act as agonistic or antagonistic ligands for members of the IL-1 receptor family; however, their biological function is presently unknown.…”

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confidence: 99%