Characterization of the Recombinant Extracellular Domains of Human Interleukin-20 Receptors and Their Complexes with Interleukin-19 and Interleukin-20

Pletnev, Sergei; Magracheva, Eugenia; Kozlov, Serguei; Tobin, Gregory J.; Kotenko, Sergei V.; Wlodawer, A.; Zdanov, Alexander

doi:10.1021/bi0354583

Cited by 47 publications

(50 citation statements)

References 29 publications

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“…This is consistent with the presumption raised for the interaction between IL-10 and IL-10 receptor. [39][40][41] According to this, binding of IL-10 to IL-10R2 requires previous binding of IL-10 to the IL-10R1 chain, leading to the creation of a binding site for IL-10R2 through conformational change of the IL-10 molecule. Regarding IL-22, our peptide scan data suggest a similar mechanism for IL-22 as for IL-10.…”

mentioning

confidence: 99%

Is there an interaction between interleukin-10 and interleukin-22?

Wolk

Witte

Reineke³

et al. 2004

Genes Immun

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Interleukin(IL)-10 and IL-22 are structurally related cytokines. Their heterodimeric receptors consist of the cytokine-specific chains IL-10R1 and IL-22R1, respectively, and the common chain IL-10R2. This study focused on the question of whether IL-10 modulates IL-22 effects and vice versa. This question is important because IL-10 and IL-22 exert anti-and proinflammatory effects, respectively, and, as we show here, are simultaneously present in both systemic and local inflammation. The revealed lacking concomitance of IL-10R1 and IL-22R1 on identical cells excluded any possible interaction between IL-10 and IL-22 apart from the competition for IL-10R2. To study this competition, monocytes and hepatocytes were chosen. The dependence of the cytokine action on IL-10R2 was verified. Interestingly, no influence of IL-22 on IL-10 effects was observed. The same was true when IL-22 was used in complex with IL-22-binding protein. Similarly, no influence of IL-10 was found on IL-22 action. This missing competition seemed to be due to a lack of binding between IL-10R2 and the native cytokines in the absence of their corresponding R1 chain. However, IL-10R2 interacted with defined IL-10-and IL-22-derived peptides supporting the hypothesis that cytokine binding to its corresponding R1 chain creates a binding site on this cytokine for IL-10R2.

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mentioning

confidence: 99%

Is there an interaction between interleukin-10 and interleukin-22?

Wolk

Witte

Reineke³

et al. 2004

Genes Immun

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“…Furthermore, IL-20 and IL-19 can both signal through type 1 IL-20 receptor complexes composed of IL-20R1 and IL-20R2 [10]. Both IL-19 and IL-20 are observed as monomers in solution, even at high protein concentration [72]. Collectively, these observations suggest that IL-20 is structurally very similar to IL-19.…”

Section: Il-20mentioning

confidence: 85%

“…Differently from IL-10 and IL-22, experimental evidence suggests that IL-19 and IL-20 display high affinity to IL-20R2, and that IL-20R1 binding occurs after the binary complex formation with the short-chain receptor (IL-20R2) [68,72]. However, the molecular basis of these events is currently unknown.…”

Section: Binary and Ternary Complexes Modelsmentioning

confidence: 99%

Structure and function of interleukin-22 and other members of the interleukin-10 family

Trivella

Ferreira-Junior

Dumoutier

et al. 2010

Cell. Mol. Life Sci.

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The IL-10 family of cytokines is comprised of IL-10, . The IL-10 family members bind to shared class II cytokine receptor chains that associate in various combinations in heterodimeric complexes. Upon interleukin/receptor complex formation, these proteins switch on the Jak/STAT pathway and elicit pleiotropic biological responses whose variety sharply contrasts with their structural similarities. IL-10 family members are involved in several human diseases and health conditions and hence their structural analyses may provide valuable information to design specific therapeutic strategies. In this review, we describe the human interleukin-10 family of cytokines, focusing on their structures and functions, with particular attention given to IL-22 and IL-10. We report on the recently published structures of IL-10 cytokine family members and their complexes with cognate transmembrane and soluble receptors as well as on interleukin physiology and physiopathology.

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“…IL-20RB associates with IL-20RA to form IL-20RI that binds IL-19, IL20 and IL-24, and IL-20RB associates with IL-22RA1 to form IL-20-RII that binds IL-20 and IL-24. 2,13,[19][20][21] After binding of the different ligands to the receptor complexes, signals are predominantly transducted via Janus kinase-signal transducer and activation of transcription pathways. 22 IL-20-RI is mainly expressed in the skin, lung and reproductive organs as well as in various glands.…”

Section: Introductionmentioning

confidence: 99%

“…The expression of IL-20-RII seems to be more restricted with high levels detectable only in the skin. 2,13,[19][20][21] There are conflicting findings with regard to the expression of IL-20R subunits in skin lesions of psoriasis.…”

Section: Introductionmentioning

confidence: 99%

Association analysis of IL20RA and IL20RB genes in psoriasis

et al. 2008

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The interleukin-20-receptor I complex (IL-20-RI) is composed of two chains, IL20RA and IL20RB. Its ligands are the three members of the IL19 subfamily of cytokines, . These cytokines are important in the manifestation of psoriatic lesions and, recently, an association of polymorphisms of IL20 with psoriasis has been described. In the present study we tested the hypotheses that genetic variations of the IL-20-RI influence susceptibility to psoriasis and investigated single nucleotide polymorphisms (SNPs) in the IL20RA and IL20RB genes in psoriasis patients (n ¼ 254) and healthy controls (n ¼ 224). We found no association of any of the investigated SNPs with the disease. Analysis of pairwise linkage disequilibrium (LD) across studied markers revealed a strong level of LD between SNPs within the IL20RA gene and SNPs within the IL20RB gene, and, for both genes six common haplotypes were identified with an estimated frequency X1%. Haplotype analyses suggested that the IL20RA haplotype CCG (rs1184860, rs1167846, rs1167849) is significantly associated with psoriasis (OR 3.14, 95% CI 1.61-6.14), whereas the TTG haplotype had a protective effect (OR 0.20, 95% CI 0.07-0.55). The risk haplotype defining SNPs 1167846 and 1184860 were found to modify paired box 5 and homeobox A9 sites, respectively, two transcription factors related to the differentiation of immune cells. Further studies are needed to confirm the genetic association and to investigate the functional relevance of IL20RA haplotypes in psoriasis.

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Characterization of the Recombinant Extracellular Domains of Human Interleukin-20 Receptors and Their Complexes with Interleukin-19 and Interleukin-20

Cited by 47 publications

References 29 publications

Is there an interaction between interleukin-10 and interleukin-22?

Is there an interaction between interleukin-10 and interleukin-22?

Structure and function of interleukin-22 and other members of the interleukin-10 family

Association analysis of IL20RA and IL20RB genes in psoriasis

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