Discovery of the DIGIRR gene from teleost fish: A novel toll-IL-1 receptor family member serving as a negative regulator of IL-1 signaling

Journal of Immunology

Volumn 187, Issue 5, 2011, Pages 2514-2530

  Gu, Yi Feng ^a,b,c   Fang, Yu ^a,b,c   Jin, Yang ^a,b,c   Dong, Wei Ren ^a,b,c   Xiang, Li Xin ^a,b,c   Shao, Jian Zhong ^a,b,c  

^a ZHEJIANG UNIVERSITY   (China)

^b Key Laboratory for Cell and Gene Engineering of Zhejiang Province   (China)

^c BEIJING HOSPITAL   (China)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IMMUNOGLOBULIN INTERLEUKIN 1 RECEPTOR RELATED MOLECULE; INTERLEUKIN 1; INTERLEUKIN 1 RECEPTOR; INTERLEUKIN 1BETA; INTERLEUKIN 6; SMALL INTERFERING RNA; TOLL LIKE RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CELLULAR DISTRIBUTION; CONTROLLED STUDY; DIGIRR GENE; EMBRYO; FEMALE; GENE; GOLGI COMPLEX; KIDNEY; LEUKOCYTE; LIVER; MALE; NONHUMAN; NUCLEOTIDE SEQUENCE; PHYLOGENY; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; TELEOST; TISSUE DISTRIBUTION; ZEBRA FISH;

ANIMALS; BASE SEQUENCE; BLOTTING, SOUTHERN; EMBRYO, NONMAMMALIAN; HUMANS; MOLECULAR SEQUENCE DATA; PHYLOGENY; RECEPTORS, INTERLEUKIN-1; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; SMEGMAMORPHA; TAKIFUGU; TETRAODONTIFORMES; TOLL-LIKE RECEPTORS; TRANSFECTION; ZEBRAFISH;

EID: 80052668568     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1003457     Document Type: Article

References (87)

1. Takeda, K., T. Kaisho, and S. Akira. 2003. Toll-like receptors. Annu. Rev. Immunol. 21: 335-376. (Pubitemid 37174535)
2. Dinarello, C. A. 1996. Biologic basis for interleukin-1 in disease. Blood 87: 2095-2147. (Pubitemid 26086851)
3. Medzhitov, R. 2001. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1: 135-145. (Pubitemid 33741967)
4. O'Neill, L. A. 2002. Toll-like receptor signal transduction and the tailoring of innate immunity: a role for Mal? Trends Immunol. 23: 296-300. (Pubitemid 34628772)
5. Kyriakis, J. M., P. Banerjee, E. Nikolakaki, T. Dai, E. A. Rubie, M. F. Ahmad, J. Avruch, and J. R. Woodgett. 1994. The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369: 156-160. (Pubitemid 24153440)
6. Ridley, S. H., S. J. Sarsfield, J. C. Lee, H. F. Bigg, T. E. Cawston, D. J. Taylor, D. L. DeWitt, and J. Saklatvala. 1997. Actions of IL-1 are selectively controlled by p38 mitogen-activated protein kinase: regulation of prostaglandin H synthase-2, metalloproteinases, and IL-6 at different levels. J. Immunol. 158: 3165-3173. (Pubitemid 127484030)
7. Bird, T. A., J. M. Kyriakis, L. Tyshler, M. Gayle, A. Milne, and G. D. Virca. 1994. Interleukin-1 activates p54 mitogen-activated protein (MAP) kinase/stress-activated protein kinase by a pathway that is independent of p21ras, Raf-1, and MAP kinase kinase. J. Biol. Chem. 269: 31836-31844.
8. Boraschi, D., and A. Tagliabue. 2006. The interleukin-1 receptor family. Vitam. Horm. 74: 229-254.
9. Alexopoulou, L., A. C. Holt, R. Medzhitov, and R. A. Flavell. 2001. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413: 732-738. (Pubitemid 33009951)
10. Hayashi, F., K. D. Smith, A. Ozinsky, T. R. Hawn, E. C. Yi, D. R. Goodlett, J. K. Eng, S. Akira, D. M. Underhill, and A. Aderem. 2001. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410: 1099-1103. (Pubitemid 32391041)
11. Takeuchi, O., K. Hoshino, T. Kawai, H. Sanjo, H. Takada, T. Ogawa, K. Takeda, and S. Akira. 1999. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 11: 443-451. (Pubitemid 29504199)
12. Ozinsky, A., D. M. Underhill, J. D. Fontenot, A. M. Hajjar, K. D. Smith, C. B. Wilson, L. Schroeder, and A. Aderem. 2000. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc. Natl. Acad. Sci. USA 97: 13766-13771.
13. Hemmi, H., O. Takeuchi, T. Kawai, T. Kaisho, S. Sato, H. Sanjo, M. Matsumoto, K. Hoshino, H. Wagner, K. Takeda, and S. Akira. 2000. A Toll-like receptor recognizes bacterial DNA. Nature 408: 740-745. (Pubitemid 32015992)
14. Hoshino, K., O. Takeuchi, T. Kawai, H. Sanjo, T. Ogawa, Y. Takeda, K. Takeda, and S. Akira. 1999. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J. Immunol. 162: 3749-3752. (Pubitemid 29314747)
15. Sims, J. E., M. A. Gayle, J. L. Slack, M. R. Alderson, T. A. Bird, J. G. Giri, F. Colotta, F. Re, A. Mantovani, K. Shanebeck, et al. 1993. Interleukin 1 signaling occurs exclusively via the type I receptor. Proc. Natl. Acad. Sci. USA 90: 6155-6159. (Pubitemid 23191473)
16. Greenfeder, S. A., P. Nunes, L. Kwee, M. Labow, R. A. Chizzonite, and G. Ju. 1995. Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J. Biol. Chem. 270: 13757-13765.
17. Parnet, P., K. E. Garka, T. P. Bonnert, S. K. Dower, and J. E. Sims. 1996. IL-1Rrp is a novel receptor-like molecule similar to the type I interleukin-1 receptor and its homologues T1/ST2 and IL-1R AcP. J. Biol. Chem. 271: 3967-3970. (Pubitemid 26074141)
18. Torigoe, K., S. Ushio, T. Okura, S. Kobayashi, M. Taniai, T. Kunikata, T. Murakami, O. Sanou, H. Kojima, M. Fujii, et al. 1997. Purification and characterization of the human interleukin-18 receptor. J. Biol. Chem. 272: 25737-25742. (Pubitemid 27438893)
19. Werenskiold, A. K., U. Rössler, M. Löwel, J. Schmidt, K. Heermeier, M. T. Spanner, and P. G. Strauss. 1995. Bone matrix deposition of T1, a homologue of interleukin 1 receptors. Cell Growth Differ. 6: 171-177.
20. Klemenz, R., S. Hoffmann, and A. K. Werenskiold. 1989. Serum- and oncoprotein-mediated induction of a gene with sequence similarity to the gene encoding carcinoembryonic antigen. Proc. Natl. Acad. Sci. USA 86: 5708-5712. (Pubitemid 19217524)
21. Thomassen, E., G. Kothny, S. Haas, J. Danescu, L. Hültner, P. Dörmer, and A. K. Werenskiold. 1995. Role of cell type-specific promoters in the developmental regulation of T1, an interleukin 1 receptor homologue. Cell Growth Differ. 6: 179-184.
22. Born, T. L., D. E. Smith, K. E. Garka, B. R. Renshaw, J. S. Bertles, and J. E. Sims. 2000. Identification and characterization of two members of a novel class of the interleukin-1 receptor (IL-1R) family. Delineation Of a new class of IL-1R-related proteins based on signaling. J. Biol. Chem. 275: 41528.
23. Lovenberg, T. W., P. D. Crowe, C. Liu, D. T. Chalmers, X. J. Liu, C. Liaw, W. Clevenger, T. Oltersdorf, E. B. De Souza, and R. A. Maki. 1996. Cloning of a cDNA encoding a novel interleukin-1 receptor related protein (IL 1R-rp2). J. Neuroimmunol. 70: 113-122. (Pubitemid 26345919)
24. Wald, D., J. Qin, Z. Zhao, Y. Qian, M. Naramura, L. Tian, J. Towne, J. E. Sims, G. R. Stark, and X. Li. 2003. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat. Immunol. 4: 920-927. (Pubitemid 37098664)
25. Thomassen, E., B. R. Renshaw, and J. E. Sims. 1999. Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily. Cytokine 11: 389-399. (Pubitemid 29259633)
26. Garlanda, C., F. Riva, N. Polentarutti, C. Buracchi, M. Sironi, M. De Bortoli, M. Muzio, R. Bergottini, E. Scanziani, A. Vecchi, et al. 2004. Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family. Proc. Natl. Acad. Sci. USA 101: 3522-3526. (Pubitemid 38338228)
27. Garlanda, C., H. J. Anders, and A. Mantovani. 2009. TIR8/SIGIRR: an IL-1R/TLR family member with regulatory functions in inflammation and T cell polarization. Trends Immunol. 30: 439-446.
28. Dinarello, C. A. 1992. Role of interleukin-1 in infectious diseases. Immunol. Rev. 127: 119-146.
29. Sims, J. E., and D. E. Smith. 2010. The IL-1 family: regulators of immunity. Nat. Rev. Immunol. 10: 89-102.
30. O'Neill, L. A., and C. A. Dinarello. 2000. The IL-1 receptor/toll-like receptor superfamily: crucial receptors for inflammation and host defense. Immunol. Today 21: 206-209. (Pubitemid 30259023)
31. Kobayashi, K., L. D. Hernandez, J. E. Galán, C. A. Janeway, Jr., R. Medzhitov, and R. A. Flavell. 2002. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110: 191-202. (Pubitemid 34876547)
32. Burns, K., S. Janssens, B. Brissoni, N. Olivos, R. Beyaert, and J. Tschopp. 2003. Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4. J. Exp. Med. 197: 263-268. (Pubitemid 36152320)
33. Kinjyo, I., T. Hanada, K. Inagaki-Ohara, H. Mori, D. Aki, M. Ohishi, H. Yoshida, M. Kubo, and A. Yoshimura. 2002. SOCS1/JAB is a negative regulator of LPS-nduced macrophage activation. Immunity 17: 583-591. (Pubitemid 35351504)
34. Colotta, F., S. K. Dower, J. E. Sims, and A. Mantovani. 1994. The type II 'decoy'receptor: a novel regulatory pathway for interleukin 1. Immunol. Today 15: 562-566. (Pubitemid 24353906)
35. Colotta, F., F. Re, M. Muzio, R. Bertini, N. Polentarutti, M. Sironi, J. G. Giri, S. K. Dower, J. E. Sims, and A. Mantovani. 1993. Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Science 261: 472-475. (Pubitemid 23276556)
36. Brint, E. K., D. Xu, H. Liu, A. Dunne, A. N. McKenzie, L. A. O'Neill, and F. Y. Liew. 2004. ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance. Nat. Immunol. 5: 373-379. (Pubitemid 38500085)
37. Wu, X. Y., L. X. Xiang, L. Huang, Y. Jin, and J. Z. Shao. 2008. Characterization, expression and evolution analysis of Toll-like receptor 1 gene in pufferfish (Tetraodon nigroviridis). Int. J. Immunogenet. 35: 215-225. (Pubitemid 351678687)
38. Roach, J. C., G. Glusman, L. Rowen, A. Kaur, M. K. Purcell, K. D. Smith, L. E. Hood, and A. Aderem. 2005. The evolution of vertebrate Toll-like receptors. Proc. Natl. Acad. Sci. USA 102: 9577-9582. (Pubitemid 40981723)
39. Meijer, A. H., S. F. Gabby Krens, I. A. Medina Rodriguez, S. He, W. Bitter, B. Ewa Snaar-Jagalska, and H. P. Spaink. 2004. Expression analysis of the Toll-like receptor and TIR domain adaptor families of zebrafish. Mol. Immunol. 40: 773-783. (Pubitemid 37542427)
40. Subramaniam, S., C. Stansberg, L. Olsen, J. Zou, C. J. Secombes, and C. Cunningham. 2002. Cloning of a Salmo salar interleukin-1 receptor-like cDNA. Dev. Comp. Immunol. 26: 415-431. (Pubitemid 34213771)
41. Zou, J., P. S. Grabowski, C. Cunningham, and C. J. Secombes. 1999. Molecular cloning of interleukin 1beta from rainbow trout Oncorhynchus mykiss reveals no evidence of an ice cut site. Cytokine 11: 552-560. (Pubitemid 29368972)
42. Huising, M. O., R. J. M. Stet, H. F. J. Savelkoul, and B. M. L. Verburg-van Kemenade. 2004. The molecular evolution of the interleukin-1 family of cytokines; IL-18 in teleost fish. Dev. Comp. Immunol. 28: 395-413. (Pubitemid 38177444)
43. Sangrador-Vegas, A., S. A. Martin, P. G. O'Dea, and T. J. Smith. 2000. Cloning and characterization of the rainbow trout (Oncorhynchus mykiss) type II interleukin-1 receptor cDNA. Eur. J. Biochem. 267: 7031-7037. (Pubitemid 32009445)
44. Stansberg, C., S. Subramaniam, B. Collet, C. J. Secombes, and C. Cunningham. 2005. Cloning of the Atlantic salmon (Salmo salar) IL-1 receptor associated protein. Fish Shellfish Immunol. 19: 53-65. (Pubitemid 40252999)
45. Stansberg, C., S. Subramaniam, L. Olsen, C. J. Secombes, and C. Cunningham. 2003. Cloning and characterisation of a putative ST2L homologue from Atlantic salmon (Salmo salar). Fish Shellfish Immunol. 15: 211-224. (Pubitemid 36990183)
46. Matsuo, A., H. Oshiumi, T. Tsujita, H. Mitani, H. Kasai, M. Yoshimizu, M. Matsumoto, and T. Seya. 2008. Teleost TLR22 recognizes RNA duplex to induce IFN and protect cells from birnaviruses. J. Immunol. 181: 3474-3485.
47. Ribeiro, C. M., T. Hermsen, A. J. Taverne-Thiele, H. F. Savelkoul, and G. F. Wiegertjes. 2010. Evolution of recognition of ligands from Gram-positive bacteria: similarities and differences in the TLR2-mediated response between mammalian vertebrates and teleost fish. J. Immunol. 184: 2355-2368.
48. Rebl, A., H. Rebl, S. Liu, T. Goldammer, and H. M. Seyfert. 2011. Salmonid Tollip and MyD88 factors can functionally replace their mammalian orthologues in TLR-mediated trout SAA promoter activation. Dev. Comp. Immunol. 35: 81-87.
49. Burge, C., and S. Karlin. 1997. Prediction of complete gene structures in human genomic DNA. J. Mol. Biol. 268: 78-94. (Pubitemid 27192680)
50. Falquet, L., M. Pagni, P. Bucher, N. Hulo, C. J. Sigrist, K. Hofmann, and A. Bairoch. 2002. The PROSITE database, its status in 2002. Nucleic Acids Res. 30: 235-238. (Pubitemid 34679552)
51. Schultz, J., F. Milpetz, P. Bork, and C. P. Ponting. 1998. SMART, a simple modular architecture research tool: identification of signaling domains. Proc. Natl. Acad. Sci. USA 95: 5857-5864. (Pubitemid 28248931)
52. Krogh, A., B. Larsson, G. Von Heijne, and E. L. Sonnhammer. 2001. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J. Mol. Biol. 305: 567-580. (Pubitemid 33032862)
53. Sonnhammer, E. L., G. Von Heijne, and A. Krogh. 1998. A hidden Markov model for predicting transmembrane helices in protein sequences. Proc. Int. Conf. Intell. Syst. Mol. Biol. 6: 175-182.
54. Bendtsen, J. D., H. Nielsen, G. Von Heijne, and S. Brunak. 2004. Improved prediction of signal peptides: SignalP 3.0. J. Mol. Biol. 340: 783-795. (Pubitemid 38829638)
55. De Castro, E., C. J. Sigrist, A. Gattiker, V. Bulliard, P. S. Langendijk-Genevaux, E. Gasteiger, A. Bairoch, and N. Hulo. 2006. ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins. Nucleic Acids Res. 34(Web Server issue): W362.
56. Thompson, J. D., D. G. Higgins, and T. J. Gibson. 1994. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22: 4673-4680. (Pubitemid 24354800)
57. Fang, W., J. Z. Shao, and L. X. Xiang. 2007. Molecular cloning and characterization of IL-15R alpha gene in rainbow trout (Oncorhynchus mykiss). Fish Shellfish Immunol. 23: 119-127. (Pubitemid 46635170)
58. Jin, H. J., L. X. Xiang, and J. Z. Shao. 2007. Molecular cloning and identification of macrophage migration inhibitory factor (MIF) in teleost fish. Dev. Comp. Immunol. 31: 1131-1144.
59. Saitou, N., and M. Nei. 1987. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4: 406-425.
60. Kumar, S., K. Tamura, and M. Nei. 2004. MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Brief. Bioinform. 5: 150-163.
61. Polentarutti, N., G. P. Rol, M. Muzio, D. Bosisio, M. Camnasio, F. Riva, C. Zoja, A. Benigni, S. Tomasoni, A. Vecchi, et al. 2003. Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8/SIGIRR. Eur. Cytokine Netw. 14: 211-218. (Pubitemid 38122227)
62. Liu, Q., U. Berchner-Pfannschmidt, U. Möller, M. Brecht, C. Wotzlaw, H. Acker, K. Jungermann, and T. Kietzmann. 2004. A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression. Proc. Natl. Acad. Sci. USA 101: 4302-4307. (Pubitemid 38405924)
63. Sepulcre, M. P., F. Alcaraz-Pérez, A. López-Muñoz, F. J. Roca, J. Meseguer, M. L. Cayuela, and V. Mulero. 2009. Evolution of lipopolysaccharide (LPS) recognition and signaling: fish TLR4 does not recognize LPS and negatively regulates NF-kappaB activation. J. Immunol. 182: 1836-1845.
64. Alcaraz-Pérez, F., V. Mulero, and M. L. Cayuela. 2008. Application of the dual-luciferase reporter assay to the analysis of promoter activity in Zebrafish embryos. BMC Biotechnol. 8: 81.
65. Elbashir, S. M., J. Harborth, K. Weber, and T. Tuschl. 2002. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods 26: 199-213. (Pubitemid 34969582)
66. Kissler, S., P. Stern, K. Takahashi, K. Hunter, L. B. Peterson, and L. S. Wicker. 2006. In vivo RNA interference demonstrates a role for Nramp1 in modifying susceptibility to type 1 diabetes. Nat. Genet. 38: 479-483.
67. Peddie, S., J. Zou, C. Cunningham, and C. J. Secombes. 2001. Rainbow trout (Oncorhynchus mykiss) recombinant IL-1beta and derived peptides induce migration of head-kidney leucocytes in vitro. Fish Shellfish Immunol. 11: 697-709. (Pubitemid 33146203)
68. Heguy, A., C. T. Baldari, G. Macchia, J. L. Telford, and M. Melli. 1992. Amino acids conserved in interleukin-1 receptors (IL-1Rs) and the Drosophila toll protein are essential for IL-1R signal transduction. J. Biol. Chem. 267: 2605-2609.
69. Ito, A., T. Takii, T. Soji, and K. Onozaki. 1997. Endotoxin-induced upregulation of type I interleukin-1 receptor mRNA expression in hepatocytes of mice: role of cytokines. J. Interferon Cytokine Res. 17: 55-61. (Pubitemid 27076282)
70. Penton-Rol, G., S. Orlando, N. Polentarutti, S. Bernasconi, M. Muzio, M. Introna, and A. Mantovani. 1999. Bacterial lipopolysaccharide causes rapid shedding, followed by inhibition of mRNA expression, of the IL-1 type II receptor, with concomitant up-regulation of the type I receptor and induction of incompletely spliced transcripts. J. Immunol. 162: 2931-2938. (Pubitemid 29309321)
71. Qin, J. Z., Y. C. Qian, J. H. Yao, C. Grace, and X. X. Li. 2005. SIGIRR inhibits interleukin-1 receptor- and toll-like receptor 4-mediated signaling through different mechanisms. J. Biol. Chem. 280: 25233-25241. (Pubitemid 40934617)
72. Schreuder, H., C. Tardif, S. Trump-Kallmeyer, A. Soffientini, E. Sarubbi, A. Akeson, T. Bowlin, S. Yanofsky, and R. W. Barrett. 1997. A new cytokine-receptor binding mode revealed by the crystal structure of the IL-1 receptor with an antagonist. Nature 386: 194-200. (Pubitemid 27131449)
73. López-Castejón, G., M. P. Sepulcre, F. J. Roca, B. Castellana, J. V. Planas, J. Meseguer, and V. Mulero. 2007. The type II interleukin-1 receptor (IL-1RII) of the bony fish gilthead seabream Sparus aurata is strongly induced after infection and tightly regulated at transcriptional and post-transcriptional levels. Mol. Immunol. 44: 2772-2780. (Pubitemid 46240309)
74. Lech, M., C. Garlanda, A. Mantovani, C. J. Kirschning, D. Schlöndorff, and H. J. Anders. 2007. Different roles of TiR8/Sigirr on toll-like receptor signaling in intrarenal antigen-presenting cells and tubular epithelial cells. Kidney Int. 72: 182-192. (Pubitemid 47067388)
75. Nasevicius, A., and S. C. Ekker. 2000. Effective targeted gene 'knockdown' in zebrafish. Nat. Genet. 26: 216-220.
76. Fire, A., S. Xu, M. K. Montgomery, S. A. Kostas, S. E. Driver, and C. C. Mello. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391: 806-811. (Pubitemid 28099681)
77. Tuschl, T., P. D. Zamore, R. Lehmann, D. P. Bartel, and P. A. Sharp. 1999. Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev. 13: 3191-3197. (Pubitemid 30030441)
78. Elbashir, S. M., J. Harborth, W. Lendeckel, A. Yalcin, K. Weber, and T. Tuschl. 2001. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411: 494-498. (Pubitemid 32494397)
79. Hannon, G. J. 2002. RNA interference. Nature 418: 244-251. (Pubitemid 34773784)
80. Sioud, M. 2004. Therapeutic siRNAs. Trends Pharmacol. Sci. 25: 22-28. (Pubitemid 38076953)
81. Brummelkamp, T. R., R. Bernards, and R. Agami. 2002. A system for stable expression of short interfering RNAs in mammalian cells. Science 296: 550-553. (Pubitemid 34408678)
82. Abbas-Terki, T., W. Blanco-Bose, N. Déglon, W. Pralong, and P. Aebischer. 2002. Lentiviral-mediated RNA interference. Hum. Gene Ther. 13: 2197-2201. (Pubitemid 36418813)
83. Aouadi, M., G. J. Tesz, S. M. Nicoloro, M. X. Wang, M. Chouinard, E. Soto, G. R. Ostroff, and M. P. Czech. 2009. Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation. Nature 458: 1180-1184.
84. De Fougerolles, A., H. P. Vornlocher, J. Maraganore, and J. Lieberman. 2007. Interfering with disease: a progress report on siRNA-based therapeutics. Nat. Rev. Drug Discov. 6: 443-453. (Pubitemid 47064567)
85. Kim, D. H., and J. J. Rossi. 2007. Strategies for silencing human disease using RNA interference. Nat. Rev. Genet. 8: 173-184.
86. Bumcrot, D., M. Manoharan, V. Koteliansky, and D. W. Sah. 2006. RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat. Chem. Biol. 2: 711-719. (Pubitemid 44764213)
87. Whitehead, K. A., R. Langer, and D. G. Anderson. 2009. Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov. 8: 129-138.