1 SUPPLEMENTAL DATA Figure S1. Poly I:C Induces IFN-Β Expression
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SUPPLEMENTAL DATA Figure S1. Poly I:C induces IFN-β expression and signaling. Fibroblasts were incubated in media with or without Poly I:C for 24 h. RNA was isolated and processed for microarray analysis. Genes showing >2-fold up- or down-regulation compared to control fibroblasts were analyzed using Ingenuity Pathway Analysis Software (Red color, up-regulation; Green color, down-regulation). The transcripts with known gene identifiers (HUGO gene symbols) were entered into the Ingenuity Pathways Knowledge Base IPA 4.0. Each gene identifier mapped in the Ingenuity Pathways Knowledge Base was termed as a focus gene, which was overlaid into a global molecular network established from the information in the Ingenuity Pathways Knowledge Base. Each network contained a maximum of 35 focus genes. 1 Figure S2. The overlap of genes regulated by Poly I:C and by IFN. Bioinformatics analysis was conducted to generate a list of 2003 genes showing >2 fold up or down- regulation in fibroblasts treated with Poly I:C for 24 h. The overlap of this gene set with the 117 skin gene IFN Core Signature comprised of datasets of skin cells stimulated by IFN (Wong et al, 2012) was generated using Microsoft Excel. 2 Symbol Description polyIC 24h IFN 24h CXCL10 chemokine (C-X-C motif) ligand 10 129 7.14 CCL5 chemokine (C-C motif) ligand 5 118 1.12 CCL5 chemokine (C-C motif) ligand 5 115 1.01 OASL 2'-5'-oligoadenylate synthetase-like 83.3 9.52 CCL8 chemokine (C-C motif) ligand 8 78.5 3.25 IDO1 indoleamine 2,3-dioxygenase 1 76.3 3.5 IFI27 interferon, alpha-inducible protein 27 70.6 40.9 TNFSF10 tumor necrosis factor (ligand) superfamily, member 10 57.2 4.83 IDO1 indoleamine 2,3-dioxygenase 1 54.1 3.01 GBP4 guanylate binding protein 4 48.1 4.97 IFIT3 interferon-induced protein with tetratricopeptide repeats 3 45.6 15.1 BST2 bone marrow stromal cell antigen 2 43.4 17.5 IL18BP interleukin 18 binding protein 43.4 9.17 TNFSF13B tumor necrosis factor (ligand) superfamily, member 13b 43.1 7.26 CFB complement factor B 41.4 5.71 IFIT2 interferon-induced protein with tetratricopeptide repeats 2 41.2 21.4 OAS1 2',5'-oligoadenylate synthetase 1, 40/46kDa 40.9 18.2 HERC5 hect domain and RLD 5 38.8 19.2 OAS2 2'-5'-oligoadenylate synthetase 2, 69/71kDa 37.7 18.5 OAS1 2',5'-oligoadenylate synthetase 1, 40/46kDa 36.9 15.2 IFIT3 interferon-induced protein with tetratricopeptide repeats 3 36 9.3 ISG20 interferon stimulated exonuclease gene 20kDa 35.6 6.15 OASL 2'-5'-oligoadenylate synthetase-like 33.8 3.18 RSAD2 radical S-adenosyl methionine domain containing 2 30.6 10.1 TNFSF13B tumor necrosis factor (ligand) superfamily, member 13b 30.5 7.57 CXCL11 chemokine (C-X-C motif) ligand 11 29.6 1.34 CD38 CD38 molecule 28 1.16 IFI6 interferon, alpha-inducible protein 6 27 19.5 MX2 myxovirus (influenza virus) resistance 2 (mouse) 25.1 16 IL6 interleukin 6 (interferon, beta 2) 24.5 2.16 TMEM171 transmembrane protein 171 24.2 1.89 IRF7 interferon regulatory factor 7 23.9 9.86 IL8 interleukin 8 23 2.26 GBP1 guanylate binding protein 1, interferon-inducible, 67kDa 22.2 4.73 IFI30 interferon, gamma-inducible protein 30 22.1 3.66 OAS3 2'-5'-oligoadenylate synthetase 3, 100kDa 21.9 12.9 SOD2 superoxide dismutase 2, mitochondrial 21.9 2.24 IFIT3 interferon-induced protein with tetratricopeptide repeats 3 21.8 12.3 IL8 interleukin 8 21 2.78 IL4I1 interleukin 4 induced 1 20.5 2.28 ISG15 ISG15 ubiquitin-like modifier 20.3 15.2 CH25H cholesterol 25-hydroxylase 20.3 2.32 IL1RN interleukin 1 receptor antagonist 19.8 -1.05 EPSTI1 epithelial stromal interaction 1 (breast) 19.5 11.5 GBP1 guanylate binding protein 1, interferon-inducible, 67kDa 19.2 4.59 HERC6 hect domain and RLD 6 19 12.6 DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 18.8 7.15 IFIT1 interferon-induced protein with tetratricopeptide repeats 1 18.7 11.6 IFI35 interferon-induced protein 35 18.5 9.91 SERPINB2 serpin peptidase inhibitor, clade B (ovalbumin), member 2 18.5 1.64 HRASLS2 HRAS-like suppressor 2 18.5 1.27 NA NA 18.3 4.17 TNFAIP6 tumor necrosis factor, alpha-induced protein 6 17.9 2.88 MX1 myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (m17.7 14.9 IL1RN interleukin 1 receptor antagonist 17.7 -1.03 SLC15A3 solute carrier family 15, member 3 17.6 6.2 TFPI2 tissue factor pathway inhibitor 2 17.5 1.28 OAS1 2',5'-oligoadenylate synthetase 1, 40/46kDa 17 7.78 SAMD9 sterile alpha motif domain containing 9 16.3 5.64 VCAM1 vascular cell adhesion molecule 1 16.3 2.31 CD68 CD68 molecule 16.2 5.48 C15orf48 chromosome 15 open reading frame 48 16 1.77 MLKL mixed lineage kinase domain-like 15.9 4.68 IFI44L interferon-induced protein 44-like 15.8 19.9 TAP1 transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) 15.7 5.63 HIST2H2AA3 histone cluster 2, H2aa3 15.7 4.42 SERPINB2 serpin peptidase inhibitor, clade B (ovalbumin), member 2 15.7 1.68 HLA-F major histocompatibility complex, class I, F 15.6 4.27 NA NA 15.5 2.31 SAMD9L sterile alpha motif domain containing 9-like 15.4 5.47 HIST2H2AA4 histone cluster 2, H2aa4 15.4 4.53 CCL2 chemokine (C-C motif) ligand 2 15.3 4.42 NA NA 15.1 1.06 GBP2 guanylate binding protein 2, interferon-inducible 14.8 4.4 BDKRB1 bradykinin receptor B1 14.6 1.86 PRIC285 peroxisomal proliferator-activated receptor A interacting complex 285 14.5 7.55 IFIT1 interferon-induced protein with tetratricopeptide repeats 1 14 3.17 RARRES3 retinoic acid receptor responder (tazarotene induced) 3 13.4 3.18 IFITM1 interferon induced transmembrane protein 1 (9-27) 13.3 9.89 TSPAN33 tetraspanin 33 13.1 3.03 CXCL9 chemokine (C-X-C motif) ligand 9 13.1 -1.02 SLC39A8 solute carrier family 39 (zinc transporter), member 8 13 2.7 TMEM140 transmembrane protein 140 12.9 4.8 BATF2 basic leucine zipper transcription factor, ATF-like 2 12.8 2.99 USP18 ubiquitin specific peptidase 18 12.6 6.1 HIST2H2AC histone cluster 2, H2ac 12.6 3.3 CXCL16 chemokine (C-X-C motif) ligand 16 12.5 3.86 NA NA 12.3 3.61 NINJ1 ninjurin 1 12.3 1.42 OAS2 2'-5'-oligoadenylate synthetase 2, 69/71kDa 12.1 4.12 STX11 syntaxin 11 12.1 1.36 LAP3 leucine aminopeptidase 3 11.9 4.89 STAT1 signal transducer and activator of transcription 1, 91kDa 11.6 6.3 LGALS9 lectin, galactoside-binding, soluble, 9 11.6 4.11 IFIH1 interferon induced with helicase C domain 1 11.4 6.42 IRF7 interferon regulatory factor 7 11.4 4.33 HIST2H2AA3 histone cluster 2, H2aa3 11.4 3.95 TNFAIP3 tumor necrosis factor, alpha-induced protein 3 11.4 1.75 GMPR guanosine monophosphate reductase 11.1 3.82 TYMP thymidine phosphorylase 11 6.03 PTGES prostaglandin E synthase 10.9 1.18 GCH1 GTP cyclohydrolase 1 10.6 1.46 IL32 interleukin 32 10.5 1.18 STAT1 signal transducer and activator of transcription 1, 91kDa 10.4 6.32 CD74 CD74 molecule, major histocompatibility complex, class II invariant chain 10.2 1.64 CXCL6 chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein 2) 10.1 2.69 RNF213 ring finger protein 213 9.91 3.79 CD34 CD34 molecule 9.86 1.89 IFI44 interferon-induced protein 44 9.75 8.75 HLA-F major histocompatibility complex, class I, F 9.57 5.02 AIM2 absent in melanoma 2 9.55 1.16 CD68 CD68 molecule 9.4 2.77 PSMB9 proteasome (prosome, macropain) subunit, beta type, 9 (large multifunctio9.27 3.3 CD68 CD68 molecule 9.26 2.34 LGMN legumain 9.23 1.98 XAF1 XIAP associated factor 1 9.14 5.07 HLA-B major histocompatibility complex, class I, B 9.12 5.94 NKX3-1 NK3 homeobox 1 9.1 1.68 SULF1 sulfatase 1 9.04 2.05 PARP14 poly (ADP-ribose) polymerase family, member 14 8.99 4.66 CMPK2 cytidine monophosphate (UMP-CMP) kinase 2, mitochondrial 8.93 4.69 ICAM2 intercellular adhesion molecule 2 8.86 1.17 LGMN legumain 8.77 2.19 PLSCR1 phospholipid scramblase 1 8.74 4.6 RTP4 receptor (chemosensory) transporter protein 4 8.71 3.55 MT1M metallothionein 1M 8.55 2.1 WARS tryptophanyl-tRNA synthetase 8.54 2.56 SLC39A8 solute carrier family 39 (zinc transporter), member 8 8.53 2.08 HAS3 hyaluronan synthase 3 8.49 1.08 C1QTNF1 C1q and tumor necrosis factor related protein 1 8.46 1.98 SLC2A6 solute carrier family 2 (facilitated glucose transporter), member 6 8.39 1.09 DHX58 DEXH (Asp-Glu-X-His) box polypeptide 58 8.34 3.77 ADAP1 ArfGAP with dual PH domains 1 8.34 1.14 TYMP thymidine phosphorylase 8.32 3.41 IL32 interleukin 32 8.31 1.24 CCL11 chemokine (C-C motif) ligand 11 8.26 1.25 TRIM22 tripartite motif-containing 22 8.22 4.85 4-Sep septin 4 8.22 1.09 SLC2A5 solute carrier family 2 (facilitated glucose/fructose transporter), member 5 8.14 1.28 SOD2 superoxide dismutase 2, mitochondrial 8.13 2.11 LOC400759 interferon-induced guanylate-binding protein 1 pseudogene 7.98 2.04 MT1G metallothionein 1G 7.98 1.64 WARS tryptophanyl-tRNA synthetase 7.95 2.83 CXCL6 chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein 2) 7.94 2.44 AGAP10 ArfGAP with GTPase domain, ankyrin repeat and PH domain 10 7.92 2.92 ZNFX1 zinc finger, NFX1-type containing 1 7.84 3.15 IL7R interleukin 7 receptor 7.78 -1.07 SRGN serglycin 7.7 1.19 SP110 SP110 nuclear body protein 7.68 3.96 FBXO6 F-box protein 6 7.66 2.78 PARP10 poly (ADP-ribose) polymerase family, member 10 7.53 4.44 NA NA 7.51 3.61 APOBEC3G apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G 7.51 2.63 MT1A metallothionein 1A 7.51 2.37 APOBEC3G apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G 7.48 2.39 NA NA 7.35 1.88 HLA-H major histocompatibility complex, class I, H (pseudogene) 7.28 3.09 BIRC3 baculoviral IAP repeat-containing 3 7.28 1.55 SLC25A28 solute carrier family 25, member 28 7.26 2.75 TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) 7.26 2.61 PARP12 poly (ADP-ribose) polymerase