Identification and Initial Characterization of Four Novel Members of the Interleukin-1 Family

Kumar, Sanjay; McDonnell, Peter; Lehr, Ruth; Tierney, Lauren A.; Tzimas, Maritsa N.; Griswold, Don E.; Capper, Elizabeth A.; Tal‐Singer, Ruth; Wells, Grace I.; Doyle, Michael L.; Young, Peter R.

doi:10.1074/jbc.275.14.10308

Cited by 312 publications

(245 citation statements)

References 44 publications

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“…However, it is clear that the cytokine IL-18 binds to both the soluble IL-18BP and the cell-bound IL-18R. A recently reported molecule, IL-1H4 (a human IL-1 homologue) has been shown to bind to IL-18R (31,32). IL-1H4 has a high degree of homology to IL-18.…”

Section: Controlmentioning

confidence: 99%

Therapeutic effect of neutralizing endogenous IL-18 activity in the collagen-induced model of arthritis

Plater-Zyberk¹,

Joosten²,

Helsen³

et al. 2001

J. Clin. Invest.

109

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Section: Controlmentioning

confidence: 99%

Therapeutic effect of neutralizing endogenous IL-18 activity in the collagen-induced model of arthritis

Plater-Zyberk¹,

Joosten²,

Helsen³

et al. 2001

J. Clin. Invest.

109

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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.…”

mentioning

confidence: 99%

“…IL37b (formerly IL-1F7b) is the last member of the IL-1 family without a well-defined function (9,10). Different from most IL-1 family members, IL-37 has emerged as an anti-inflammatory cytokine.…”

mentioning

confidence: 99%

Interleukin 37 expression protects mice from colitis

McNamee

Masterson

Jedlicka

et al. 2011

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

293

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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“…The recent identification of closely related ligands that also bind to the IL-1␤R contributes to the complexity of this family of proteins. These include new receptor antagonists for IL-1␤, such as IL-1HY1 and IL-1HY2, and other novel ligands, such as IL-1H1-H4 (22)(23)(24)(25). IL-1 activity, which is usually imparted by IL-1␣ and IL-1␤ via the IL-1R, seems to be a tightly regulated process.…”

Section: Discussionmentioning

confidence: 99%

Functional Genomic Analysis of Type II IL-1β Decoy Receptor: Potential for Gene Therapy in Human Arthritis and Inflammation

Attur

Dave

Leung

et al. 2002

The Journal of Immunology

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Gene expression arrays show that human epithelial cells and human arthritis-affected cartilage lack detectable amounts of mRNA for IL-1 antagonizing molecules: IL-1Ra and IL-1RII, but constitutively express IL-1. Functional genomic analysis was performed by reconstituting human IL-1RII expression in various IL-1RII-deficient cell types to examine its antagonist role using gene therapy approaches. Adenovirus-expressing IL-1RII when transduced into human and bovine chondrocytes, human and rabbit synovial cells, human epithelial cells, and rodent fibroblasts expressed membrane IL-1RII and spontaneously released functional soluble IL-1RII. The IL-1RII+ (but not IL-1RII−) cells were resistant to IL-1β-induced, NO, PGE2, IL-6, and IL-8 production or decreased proteoglycan synthesis. IL-1RII inhibited the function of IL-1 in chondrocytes and IL-1- and TNF-α-induced inflammatory mediators in human synovial and epithelial cells. IL-1RII+ chondrocytes were more resistant to induction of NO and PGE2 by IL-1β compared with IL-1RII− cells incubated with a 10-fold (weight) excess of soluble type II IL-1R (sIL-1RII) protein. In cocultures, IL-1RII+ synovial cells released sIL-1RII, which in a paracrine fashion protected chondrocytes from the effects of IL-1β. Furthermore, IL-1RII+ (but not IL-1RII−) chondrocytes when transplanted onto human osteoarthritis-affected cartilage in vitro, which showed spontaneous release of sIL-1RII for 20 days, inhibited the spontaneous production of NO and PGE2 in cartilage in ex vivo. In summary, reconstitution of IL-1RII in IL-1RII− cells using gene therapy approaches significantly protects cells against the autocrine and paracrine effects of IL-1 at the signaling and transcriptional levels.

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Identification and Initial Characterization of Four Novel Members of the Interleukin-1 Family

Cited by 312 publications

References 44 publications

Therapeutic effect of neutralizing endogenous IL-18 activity in the collagen-induced model of arthritis

Therapeutic effect of neutralizing endogenous IL-18 activity in the collagen-induced model of arthritis

Interleukin 37 expression protects mice from colitis

Functional Genomic Analysis of Type II IL-1β Decoy Receptor: Potential for Gene Therapy in Human Arthritis and Inflammation

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