Characterisation and expression analysis of the Atlantic halibut (Hippoglossus hippoglossus L.) cytokines: IL-1β, IL-6, IL-11, IL-12β and IFNγ

Molecular Biology Reports

Volumn 39, Issue 3, 2012, Pages 2201-2213

  Øvergård, Aina Cathrine ^a,b   Nepstad, Ina ^a,b,c   Nerland, Audun Helge ^a   Patel, Sonal ^a  

^a INSTITUTE OF MARINE RESEARCH   (Norway)

^b UNIVERSITY OF BERGEN   (Norway)

^c HAUKELAND UNIVERSITY HOSPITAL   (Norway)

Author keywords

Fish; Imiquimod; Interferon; Interleukin; Teleost

Indexed keywords

COMPLEMENTARY DNA; GAMMA INTERFERON; IMIQUIMOD; INTERLEUKIN 11; INTERLEUKIN 12P40; INTERLEUKIN 1BETA; INTERLEUKIN 6; MESSENGER RNA; PEPTIDE;

3' UNTRANSLATED REGION; AMINO ACID SEQUENCE; ANIMAL CELL; ARTICLE; CYTOKINE GENE; DNA SEQUENCE; FLATFISH; GENE; GENE EXPRESSION; GENETIC CONSERVATION; GENETIC ORGANIZATION; GILL; HIPPOGLOSSUS HIPPOGLOSSUS; IN VITRO STUDY; INTESTINE; KIDNEY; LEUKOCYTE ACTIVATION; LYMPHOID ORGAN; MOLECULAR CLONING; MOLECULAR GENETICS; NONHUMAN; NUCLEOTIDE SEQUENCE; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN MOTIF; PROTEIN SECONDARY STRUCTURE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA STABILITY; SEQUENCE HOMOLOGY; THYMUS;

ANIMALS; BASE SEQUENCE; CLONING, MOLECULAR; COMPUTATIONAL BIOLOGY; CYTOKINES; DNA PRIMERS; DNA, COMPLEMENTARY; FLOUNDER; INTERFERON-GAMMA; INTERLEUKIN-11; INTERLEUKIN-12 SUBUNIT P40; INTERLEUKIN-1BETA; INTERLEUKIN-6; MOLECULAR SEQUENCE DATA; REAL-TIME POLYMERASE CHAIN REACTION; SEQUENCE ANALYSIS, DNA; SPECIES SPECIFICITY; STATISTICS, NONPARAMETRIC;

AVES; HIPPOGLOSSUS HIPPOGLOSSUS; MAMMALIA; TELEOSTEI;

EID: 84863311157     PISSN: 03014851     EISSN: 15734978     Source Type: Journal    
DOI: 10.1007/s11033-011-0969-x     Document Type: Article

References (99)

1. Bergh Ø, Nilsen F, Samuelsen OB (2001) Diseases, prophylaxis and treatment of the Atlantic halibut Hippoglossus hippoglossus: a review. Dis Aquat Organ 48:57-74
2. Patel S, Malde K, Lanzen A, Olsen RH, Nerland AH (2009) Identification of immune related genes in Atlantic halibut (Hippoglossus hippoglossus L.) following in vivo antigenic and in vitro mitogenic stimulation. Fish Shellfish Immunol 27:729-738
3. Buonocore F, Prugnoli D, Falasca C, Secombes CJ, Scapigliati G (2003) Peculiar gene organisation and incomplete splicing of sea bass (Dicentrarchus labrax L.) interleukin-1beta. Cytokine 21:257-264
4. Corripio-Miyar Y, Bird S, Tsamopoulos K, Secombes CJ (2007) Cloning and expression analysis of two pro-inflammatory cytokines, IL-1 beta and IL-8, in haddock (Melanogrammus aeglefinus). Mol Immunol 44:1361-1373
5. Fujiki K, Shin DH, Nakao M, Yano T (2000) Molecular cloning and expression analysis of carp (Cyprinus carpio) interleukin-1 beta, high affinity immunoglobulin E Fc receptor gamma subunit and serum amyloid A. Fish Shellfish Immunol 10:229-242
6. Lee DS, Hong SH, Lee HJ, Jun LJ, Chung JK, Kim KH et al (2006) Molecular cDNA cloning and analysis of the organization and expression of the IL-1beta gene in the Nile tilapia, Oreochromis niloticus. Comp Biochem Physiol A Mol Integr Physiol 143:307-314
7. Lu DQ, Bei JX, Feng LN, Zhang Y, Liu XC, Wang L et al (2008) Interleukin-1beta gene in orange-spotted grouper, Epinephelus coioides: molecular cloning, expression, biological activities and signal transduction. Mol Immunol 45:857-867
8. Pelegrin P, Garcia-Castillo J, Mulero V, Meseguer J (2001) Interleukin-1beta isolated from a marine fish reveals up-regulated expression in macrophages following activation with lipopolysaccharide and lymphokines. Cytokine 16:67-72
9. Pleguezuelos O, Zou J, Cunningham C, Secombes CJ (2000) Cloning, sequencing, and analysis of expression of a second IL- 1beta gene in rainbow trout (Oncorhynchus mykiss). Immunogenetics 51:1002-1011
10. Scapigliati G, Buonocore F, Bird S, Zou J, Pelegrin P, Falasca C et al (2001) Phylogeny of cytokines: molecular cloning and expression analysis of sea bass Dicentrarchus labrax interleukin- 1beta. Fish Shellfish Immunol 11:711-726
11. Seppola M, Larsen AN, Steiro K, Robertsen B, Jensen I (2008) Characterisation and expression analysis of the interleukin genes, IL-1beta, IL-8 and IL-10, in Atlantic cod (Gadus morhua L.). Mol Immunol 45:887-897
12. Zou J, Grabowski PS, Cunningham C, Secombes CJ (1999) Molecular cloning of interleukin 1beta from rainbow trout Oncorhynchus mykiss reveals no evidence of an ice cut site. Cytokine 11:552-560
13. Wang Y, Wang Q, Baoprasertkul P, Peatman E, Liu Z (2006) Genomic organization, gene duplication, and expression analysis of interleukin-1beta in channel catfish (Ictalurus punctatus). Mol Immunol 43:1653-1664
14. Zou J, Holland J, Pleguezuelos O, Cunningham C, Secombes CJ (2000) Factors influencing the expression of interleukin-1 beta in cultured rainbow trout (Oncorhynchus mykiss) leucocytes. Dev Comp Immunol 24:575-582
15. Buonocore F, Forlenza M, Randelli E, Benedetti S, Bossu P, Meloni S et al (2005) Biological activity of sea bass (Dicentrarchus labrax L.) recombinant interleukin-1beta. Mar Biotechnol (NY) 7:609-617
16. Jorgensen JB, Zou J, Johansen A, Secombes CJ (2001) Immunostimulatory CpG oligodeoxynucleotides stimulate expression of IL-1beta and interferon-like cytokines in rainbow trout macrophages via a chloroquine-sensitive mechanism. Fish Shellfish Immunol 11:673-682
17. Poisa-Beiro L, Dios S, Montes A, Aranguren R, Figueras A, Novoa B (2008) Nodavirus increases the expression of Mx and inflammatory cytokines in fish brain. Mol Immunol 45:218-225
18. Engelsma MY, Stet RJ, Saeij JP, Lidy Verburg-van Kemenade BM (2003) Differential expression and haplotypic variation of two interleukin-1beta genes in the common carp (Cyprinus carpio L.). Cytokine 22:21-32
19. Hong S, Zou J, Crampe M, Peddie S, Scapigliati G, Bols N et al (2001) The production and bioactivity of rainbow trout (Oncorhynchus mykiss) recombinant IL-1 beta. Vet Immunol Immunopathol 81:1-14
20. Peddie S, Zou J, Cunningham C, Secombes CJ (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
21. Secombes CJ, Wang T, Hong S, Peddie S, Crampe M, Laing KJ et al (2001) Cytokines and innate immunity of fish. Dev Comp Immunol 25:713-723
22. Peddie S, Zou J, Secombes CJ (2002) A biologically active IL-1b derived peptide stimulates phagocytosis and bacterial activity in rainbow trout, Oncorhynchus mykiss (Walbaum), head kidney leucocytes in vitro. J Fish Dis 25:351-360
23. Hong S, Peddie S, Campos-Perez JJ, Zou J, Secombes CJ (2003) The effect of intraperitoneally administered recombinant IL- 1beta on immune parameters and resistance to Aeromonas salmonicida in the rainbow trout (Oncorhynchus mykiss). Dev Comp Immunol 27:801-812
24. Buonocore F, Mazzini M, Forlenza M, Randelli E, Secombes CJ, Zou J et al (2004) Expression in Escherchia coli and purification of sea bass (Dicentrarchus labrax) interleukin 1beta, a possible immunoadjuvant in aquaculture. Mar Biotechnol (NY) 6:53-59
25. Bird S, Zou J, Savan R, Kono T, Sakai M, Woo J et al (2005) Characterisation and expression analysis of an interleukin 6 homologue in the Japanese pufferfish, Fugu rubripes. Dev Comp Immunol 29:775-789
26. Nam BH, Byon JY, Kim YO, Park EM, Cho YC, Cheong J (2007) Molecular cloning and characterisation of the flounder (Paralichthys olivaceus) interleukin-6 gene. Fish Shellfish Immunol 23:231-236
27. Iliev DB, Castellana B, Mackenzie S, Planas JV, Goetz FW (2007) Cloning and expression analysis of an IL-6 homolog in rainbow trout (Oncorhynchus mykiss). Mol Immunol 44:1803-1807
28. Castellana B, Iliev DB, Sepulcre MP, MacKenzie S, Goetz FW, Mulero V et al (2008) Molecular characterization of interleukin-6 in the gilthead seabream (Sparus aurata). Mol Immunol 45:3363-3370
29. Huising MO, Kruiswijk CP, van Schijndel JE, Savelkoul HF, Flik G, Lidy Verburgvan Kemenade BM (2005) Multiple and highly divergent IL-11 genes in teleost fish. Immunogenetics 57:432-443
30. Wang T, Holland JW, Bols N, Secombes CJ (2005) Cloning and expression of the first nonmammalian interleukin-11 gene in rainbow trout Oncorhynchus mykiss. FEBS J 272:1136-1147
31. Santos MD, Yasuike M, Kondo H, Hirono I, Aoki T (2008) Teleostean IL11b exhibits complementing function to IL11a and expansive involvement in antibacterial and antiviral responses. Mol Immunol 45:3494-3501
32. Huising MO, van Schijndel JE, Kruiswijk CP, Nabuurs SB, Savelkoul HF, Flik G et al (2006) The presence of multiple and differentially regulated interleukin-12p40 genes in bony fishes signifies an expansion of the vertebrate heterodimeric cytokine family. Mol Immunol 43:1519-1533
33. Nascimento DS, do Vale A, Tomas AM, Zou J, Secombes CJ, dos Santos NM (2007) Cloning, promoter analysis and expression in response to bacterial exposure of sea bass (Dicentrarchus labrax L.) interleukin-12 p40 and p35 subunits. Mol Immunol 44:2277-2291
34. Yoshiura Y, Kiryu I, Fujiwara A, Suetake H, Suzuki Y, Nakanishi T et al (2003) Identification and characterization of Fugu orthologues of mammalian interleukin-12 subunits. Immunogenetics 55:296-306
35. Igawa D, Sakai M, Savan R (2006) An unexpected discovery of two interferon gamma-like genes along with interleukin (IL)-22 and -26 from teleost: IL-22 and -26 genes have been described for the first time outside mammals. Mol Immunol 43:999-1009
36. Zou J, Yoshiura Y, Dijkstra JM, Sakai M, Ototake M, Secombes C (2004) Identification of an interferon gamma homologue in Fugu, Takifugu rubripes. Fish Shellfish Immunol 17:403-409
37. Zou J, Carrington A, Collet B, Dijkstra JM, Yoshiura Y, Bols N et al (2005) Identification and bioactivities of IFN-gamma in rainbow trout Oncorhynchus mykiss: the first Th1-type cytokine characterized functionally in fish. J Immunol 175:2484-2494
38. Milev-Milovanovic I, Long S, Wilson M, Bengten E, Miller NW, Chinchar VG (2006) Identification and expression analysis of interferon gamma genes in channel catfish. Immunogenetics 58:70-80
39. Stolte EH, Savelkoul HF, Wiegertjes G, Flik G, Lidy Verburgvan Kemenade BM (2008) Differential expression of two interferon- gamma genes in common carp (Cyprinus carpio L.). Dev Comp Immunol 32:1467-1481
40. Furnes C, Seppola M, Robertsen B (2009) Molecular characterisation and expression analysis of interferon gamma in Atlantic cod (Gadus morhua). Fish Shellfish Immunol 26:285-292
41. Grayfer L, Belosevic M (2009) Molecular characterization, expression and functional analysis of goldfish (Carassius aurutus L.) interferon gamma. Dev Comp Immunol 33:235-246
42. Boschi I, Randelli E, Buonocore F, Casani D, Fausto AM, Scapigliati G (2010) Transcription of T cell-related genes in teleost fish, and the European sea bass (Dicentrarchus labrax) as a model. Fish Shellfish Immunol. doi:10.1016/j.fsi.2010.10.001
43. Purcell MK, Laing KJ, Woodson JC, Thorgaard GH, Hansen JD (2009) Characterization of the interferon genes in homozygous rainbow trout reveals two novel genes, alternate splicing and differential regulation of duplicated genes. Fish Shellfish Immunol 26:293-304
44. Dockrell DH, Kinghorn GR (2001) Imiquimod and resiquimod as novel immunomodulators. J Antimicrob Chemother 48:751-755
45. Øverland HS, Pettersen EF, Rønneseth A, Wergeland HI (2010) Phagocytosis by B-cells and neutrophils in Atlantic salmon (Salmo salar L.) and Atlantic cod (Gadus morhua L.). Fish Shellfish Immunol 28:193-204
46. Patel S, Øvergård AC, Nerland AH (2008) CD8a and CD8b in Atlantic halibut, Hippoglossus hippoglossus: cloning, characterization and gene expression during viral and bacterial infection. Fish Shellfish Immunol 25:570-580
47. Øvergård AC, Nerland AH, Patel S (2010) Evaluation of potential reference genes for real time RT-PCR studies in Atlantic halibut (Hippoglossus Hippoglossus L.); during development, in tissues of healthy and NNV-injected fish, and in anterior kidney leucocytes. BMC Mol Biol 11:36
48. Patel S, Øvergård AC, Nerland AH (2009) A CD4 homologue in Atlantic halibut (Hippoglossus hippoglossus): molecular cloning and characterisation. Fish Shellfish Immunol 26:377-384
49. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-DDCt Method. Methods 25:402-408
50. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45
51. Engelsma MY, Stet RJ, Schipper H, Lidy Verburg-van Kemenade BM (2001) Regulation of interleukin 1 beta RNA expression in the common carp, Cyprinus carpio L. Dev Comp Immunol 25:195-203
52. Clark BD, Collins KL, Gandy MS, Webb AC, Auron PE (1986) Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene. Nucleic Acids Res 14:7897-7914
53. Zou J, Cunningham C, Secombes CJ (1999) The rainbow trout Oncorhynchus mykiss interleukin-1 beta gene has a differ organization to mammals and undergoes incomplete splicing. Eur J Biochem 259:901-908
54. Sachs AB (1993) Messenger RNA degradation in eukaryotes. Cell 74:413-421
55. Labriola-Tompkins E, Chandran C, Kaffka KL, Biondi D, Graves BJ, Hatada M et al (1991) Identification of the discontinuous binding site in human interleukin 1 beta for the type I interleukin 1 receptor. Proc Natl Acad Sci USA 88:11182-11186
56. Miller DK, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Molineaux SM et al (1993) The IL-1 beta converting enzyme as a therapeutic target. Ann NY Acad Sci 696:133-148
57. Rubartelli A, Cozzolino F, Talio M, Sitia R (1990) A novel secretory pathway for interleukin-1 beta, a protein lacking a signal sequence. EMBO J 9:1503-1510
58. MacKenzie A, Wilson HL, Kiss-Toth E, Dower SK, North RA, Surprenant A (2001) Rapid secretion of interleukin-1beta by microvesicle shedding. Immunity 15:825-835
59. Bird S, Zou J, Wang T, Munday B, Cunningham C, Secombes CJ (2002) Evolution of interleukin-1beta. Cytokine Growth Factor Rev 13:483-502
60. Hong S, Zou J, Collet B, Bols NC, Secombes CJ (2004) Analysis and characterisation of IL-1beta processing in rainbow trout, Oncorhynchus mykiss. Fish Shellfish Immunol 16:453-459
61. Pelegrin P, Chaves-Pozo E, Mulero V, Meseguer J (2004) Production and mechanism of secretion of interleukin-1beta from the marine fish gilthead seabream. Dev Comp Immunol 28:229-237
62. Kavita U, Mizel SB (1995) Differential sensitivity of interleukin- 1a and -b precursor proteins to cleavage by calpain, a calsium dependent protease. J Biol Chem 270:27758-27765
63. Tanabe O, Akira S, Kamiya T, Wong GG, Hirano T, Kishimoto T (1988) Genomic structure of the murine IL-6 gene. High degree conservation of potential regulatory sequences between mouse and human. J Immunol 141:3875-3881
64. Yasukawa K, Hirano T, Watanabe Y, Muratani K, Matsuda T, Nakai S et al (1987) Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene. EMBO J 6:2939-2945
65. Somers W, Stahl M, Seehra JS (1997) 1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling. EMBO J 16:989-997
66. Skelly SM, Tackney C, Hicklin D, Tamkins T, Goldstein N, Waksal H et al (1994) High-level expression of a biologically active human interleukin-6 mutein. J Biotechnol 34:79-86
67. Simpson RJ, Hammacher A, Smith DK, Matthews JM, Ward LD (1997) Interleukin-6: structure-function relationships. Protein Sci 6:929-955
68. Barton VA, Hudson KR, Heath JK (1999) Identification of three distinct receptor binding sites of murine interleukin-11. J Biol Chem 274:5755-5761
69. Balu S, Kaiser P (2003) Avian interleukin-12beta (p40): cloning and characterization of the cDNA and gene. J Interferon Cytokine Res 23:699-707
70. Yoon C, Johnston SC, Tang J, Stahl M, Tobin JF, Somers WS (2000) Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12. EMBO J 19:3530-3541
71. Kaiser P, Wain HM, Rothwell L (1998) Structure of the chicken interferon-gamma gene, and comparison to mammalian homologues. Gene 207:25-32
72. Thiel DJ, le Du MH, Walter RL, D'Arcy A, Chene C, Fountoulakis M et al (2000) Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex. Structure 8:927-936
73. Hansen JD, Zapata AG (1998) Lymphocyte development in fish and amphibians. Immunol Rev 166:199-220
74. Bodey B (2007) Thymic reticulo-epithelial cells: key cells of neuroendocrine regulation. Expert Opin Biol Ther 7:939-949
75. Rodriguez-Galan MC, Bream JH, Farr A, Young HA (2005) Synergistic effect of IL-2, IL-12, and IL-18 on thymocyte apoptosis and Th1/Th2 cytokine expression. J Immunol 174:2796-2804
76. Lagrota-Candido JM, Villa-Verde DM, Vanderlei FH Jr, Savino W (1996) Extracellular matrix components of the mouse thymus microenvironment. V. Interferon-gamma modulates thymic epithelial cell/thymocyte interactions via extracellular matrix ligands and receptors. Cell Immunol 170:235-244
77. Ransom J, Fischer M, Mosmann T, Yokota T, DeLuca D, Schumacher J et al (1987) Interferon-gamma is produced by activated immature mouse thymocytes and inhibits the interleukin 4-induced proliferation of immature thymocytes. J Immunol 139:4102-4108
78. Mukamoto M, Kodama H, Baba T (1999) Effects of cytokines from thymocytes and thymic stromal cells on chicken intrathymic T cell development. Vet Immunol Immunopathol 67:223-233
79. Deman J, Van Meurs M, Claassen E, Humblet C, Boniver J, Defresne MP (1996) In vivo expression of interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-6, tumour necrosis factor-alpha and interferongamma in the fetal murine thymus. Immunology 89:152-157
80. Øvergård AC, Hordvik I, Nerland AH, Eikeland G, Patel S (2009) Cloning and expression analysis of Atlantic halibut (Hippoglossus hippoglossus) CD3 genes. Fish Shellfish Immunol 27:707-713
81. Øvergård AC, Nerland AH, Patel S (2010) Cloning, characterization, and expression pattern of Atlantic halibut (Hippoglossus hippoglossus L.) CD4-2, Lck, and ZAP-70. Fish Shellfish Immunol 29:987-997
82. Patel S, Sørhus E, Fiksdal IU, Espedal PG, Bergh Ø, Rødseth OM et al (2009) Ontogeny of lymphoid organs and development of IgM-bearing cells in Atlantic halibut (Hippoglossus hippoglossus L.). Fish Shellfish Immunol 26:385-395
83. Øvergård AC, Fiksdal IU, Nerland AH, Patel S (2011) Expression of T-cell markers during Atlantic halibut (Hippoglossus hippoglossus L.) ontogenesis. Dev Comp Immunol 35:203-213
84. Haugarvoll E, Bjerkas I, Nowak BF, Hordvik I, Koppang EO (2008) Identification and characterization of a novel intraepithelial lymphoid tissue in the gills of Atlantic salmon. J Anat 213:202-209
85. Koppang EO, Fischer U, MooreL,TranulisMA,Dijkstra JM,Kollner B et al (2010) Salmonid T cells assemble in the thymus, spleen and in novel interbranchial lymphoid tissue. J Anat 217:728-739
86. Taga T, Fukuda S (2005) Role of IL-6 in the neural stem cell differentiation. Clin Rev Allergy Immunol 28:249-256
87. Mastorakos G, Ilias I (2006) Interleukin-6: a cytokine and/or a major modulator of the response to somatic stress. Ann NY Acad Sci 1088:373-381
88. Nandurkar HH, Robb L, Begley CG (1998) The role of IL-II in hematopoiesis as revealed by a targeted mutation of its receptor. Stem Cells 16(Suppl 2):53-65
89. Press CM, Evensen O (1999) The morphology of the immune system in teleost fishes. Fish Shellfish Immunol 9:309-318
90. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K et al (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3:196-200
91. Hayashi F, Means TK, Luster AD (2003) Toll-like receptors stimulate human neutrophil function. Blood 102:2660-2669
92. Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdorfer B, Giese T et al (2002) Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol 168:4531-4537
93. Liu YJ (2005) IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol 23:275-306
94. Testerman TL, Gerster JF, Imbertson LM, Reiter MJ, Miller RL, Gibson SJ et al (1995) Cytokine induction by the immunomodulators imiquimod and S-27609. J Leukoc Biol 58:365-372
95. Gibson SJ, Lindh JM, Riter TR, Gleason RM, Rogers LM, Fuller AE et al (2002) Plasmacytoid dendritic cells produce cytokines and mature in response to the TLR7 agonists, imiquimod and resiquimod. Cell Immunol 218:74-86
96. Wagner TL, Ahonen CL, Couture AM, Gibson SJ, Miller RL, Smith RM et al (1999) Modulation of TH1 and TH2 cytokine production with the immune response modifiers, R-848 and imiquimod. Cell Immunol 191:10-19
97. Kileng O, Albuquerque A, Robertsen B (2008) Induction of interferon system genes in Atlantic salmon by the imidazoquinoline S-27609, a ligand for Toll-like receptor 7. Fish Shellfish Immunol 24:514-522
98. Purcell MK, Smith KD, Hood L, Winton JR, Roach JC (2006) Conservation of toll-like receptor signaling pathways in teleost fish. Comp Biochem Physiol D Genomics Proteomics 1:77-88
99. Tanekhy M, Kono T, Sakai M (2010) Cloning, characterization, and expression analysis of Toll-like receptor-7 cDNA from common carp, Cyprinus carpio L. Comp Biochem Physiol D Genomics Proteomics 5:245-255