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Maren Depke Results Gene Expression Pattern of Bone-Marrow Derived Macrophages after Interferon-gamma Treatment found to be repressed. Finally, differential expression was observed for members of the TNF ligand and receptor superfamilies. The central inflammation mediator Tnf, the apoptosis inducer TRAIL (Tnfsf10), and the T cell survival modulator Tnfsf18 were induced in parallel with the receptor Tnfrsf14 (Table R.3.5). Table R.3.5: IFN-γ influence on gene expression of cytokines and cytokine receptors in BMM of BALB/c and C57BL/6 mice. Rosetta Resolver Annotation fold change a strain difference gene Entrez description alias name Gene ID BALB/c C57BL/6 control IFN-γ Ccl5 chemokine (C-C motif) ligand 5 SISd, Scya5, RANTES, TCP228 20304 3.7 5.0 Ccl12 chemokine (C-C motif) ligand 12 MCP-5, Scya12 20293 3.4 2.1 Ccl22 chemokine (C-C motif) ligand 22 MDC, DCBCK, ABCD-1, Scya22 20299 2.9 3.6 Ccr5 chemokine (C-C motif) receptor 5 AM4-7, CD195, Cmkbr5 12774 1.7 1.4 Ccrl2 chemokine (C-C motif) receptor-like 2 E01, CCR11, L-CCR, Cmkbr1l2 54199 2.0 1.7 Cxcl9 chemokine (C-X-C motif) ligand 9 CMK, Mig, Scyb9, crg-10 17329 45.0 56.1 Cxcl10 chemokine (C-X-C motif) ligand 10 C7, IP10, CRG-2, INP10, Ifi10, mob-1, Scyb10, 15945 47.8 21.5 gIP-10 Cxcl11 chemokine (C-X-C motif) ligand 11 IP9, H174, ITAC, CXC11, SCYB9B, Scyb11, betaR1 56066 8.3 1.1 x Cxcl16 chemokine (C-X-C motif) ligand 16 SR-PSOX, Zmynd15 66102 2.6 2.9 Cxcr4 chemokine (C-X-C motif) receptor 4 CD184, LESTR, Sdf1r, Cmkar4, PB-CKR, 12767 -1.8 -2.2 x x PBSF/SDF-1 Il1rl2 interleukin 1 receptor-like 2 IL-1Rrp2 107527 -1.7 -1.8 Il2rg interleukin 2 receptor, gamma chain CD132, gamma(c) 16186 1.9 1.7 Il4ra interleukin 4 receptor, alpha Il4r, CD124 16190 2.0 1.6 x x Il6st interleukin 6 signal transducer CD130, gp130 16195 -1.8 -1.8 Il10ra interleukin 10 receptor, alpha Il10r, CDw210, mIL-10R 16154 1.6 1.7 Il12rb1 interleukin 12 receptor, beta 1 CD212, IL-12R[b] 16161 1.8 3.9 Il13ra1 interleukin 13 receptor, alpha 1 NR4, Il13ra, CD213a1 16164 2.1 1.7 x Il15 interleukin 15 16168 2.8 2.0 x Il15ra interleukin 15 receptor, alpha chain 16169 4.3 4.0 Il18bp interleukin 18 binding protein MC54L, Igifbp, IL-18BP 16068 5.5 6.2 Il21r interleukin 21 receptor NILR 60504 3.4 2.8 x x Il27 interleukin 27 p28, Il30, IL-27p28 246779 2.3 2.4 Tnf tumor necrosis factor DIF, Tnfa, TNFSF2, Tnfsf1a, TNF-alpha 21926 2.4 2.7 Tnfsf10 tumor necrosis factor (ligand) superfamily, member 10 TL2, Ly81, Trail, APO-2L 22035 10.6 5.2 Tnfsf18 tumor necrosis factor (ligand) superfamily, member 18 Gitrl 240873 3.3 1.1 x Tnfrsf14 tumor necrosis factor receptor superfamily, Atar, HveA, Hvem, member 14 (herpesvirus entry mediator) Tnfrs14 230979 2.6 2.5 a Fold change values were calculated from expression intensities of IFN-γ treated BMM in comparison to control BMM from the mean of three biological replicates. Differential expression in statistical testing with p* < 0.01 and a minimal absolute fold change of 1.5 is indicated in bold. Furthermore, GTPases / GTP binding proteins of different families, which are known to be induced by interferon and play a role in antimicrobial defense, were induced, and some even belonged to the genes with the strongest induction within the data set. Four families are described in literature (MacMicking 2004), p47 GTPases, p65 guanylate-binding proteins (GBP), Mx proteins and very large inducible GTPases (VLIG), and of each family examples were included in the data set of induced genes in BMM after IFN-γ treatment. The p47 family was present with the members Igtp, Iigp1, Irgm1, and Tgtp. All guanylate binding proteins of the p65 family were induced (Gbp1, Gbp2, Gbp3, Gbp4, Gbp5, and Gbp6). Both types of Mx genes, coding for the nuclear (Mx1) and the cytosolic (Mx2) form, exhibited increased expression in BMM after IFN-γ treatment. Finally, very large interferon inducible GTPase 1, Gvin1, was included in the list of induced genes as member of the last family (Table R.3.6). 100
Maren Depke Results Gene Expression Pattern of Bone-Marrow Derived Macrophages after Interferon-gamma Treatment Table R.3.6: IFN-γ influence on gene expression of GTPase family members in BMM of BALB/c and C57BL/6 mice. Rosetta Resolver Annotation fold change a strain difference gene Entrez description alias name Gene ID BALB/c C57BL/6 control IFN-γ Igtp interferon gamma induced GTPase Irgm3 16145 17.4 13.5 Iigp1 interferon inducible GTPase 1 Iigp, Irga6 60440 100.0 100.0 Irgm1 immunity-related GTPase family M member 1 Ifi1, Irgm, Iigp3, Iipg3, LRG-47 15944 6.9 11.2 Tgtp T-cell specific GTPase Tgtp, Gtp2, Mg21, Irgb6 21822 49.0 100.0 Gbp1 guanylate binding protein 1 Mpa1, Gbp-1, Mag-1 14468 43.9 6.0 x x Gbp2 guanylate binding protein 2 14469 17.2 31.2 x Gbp3 guanylate binding protein 3 Gbp4 55932 21.7 15.6 Gbp4 guanylate binding protein 4 Mpa2, Mag-2, Mpa-2 17472 60.6 94.3 Gbp5 guanylate binding protein 5 Gbp5a 229898 50.7 66.8 Gbp6 guanylate binding protein 6 Gbp7 229900 9.3 7.2 Mx1 myxovirus (influenza virus) resistance 1 Mx, Mx-1 17857 10.8 6.9 x Mx2 myxovirus (influenza virus) resistance 2 Mx-2 17858 6.1 3.5 x Gvin1 GTPase, very large interferon inducible 1 VLIG, Iigs1, VLIG-1 74558 4.6 6.7 a Fold change values were calculated from expression intensities of IFN-γ treated BMM in comparison to control BMM from the mean of three biological replicates. Differential expression in statistical testing with p* < 0.01 and a minimal absolute fold change of 1.5 is indicated in bold. BMM after IFN-γ treatment induced the expression of complement system components. Of the classical activation pathway, the C1 subcomponents C1qa, C1qb, C1qc, C1r, and C1rb were induced, and of the alternative pathway factor B (Cfb). Induced component C3 takes part in all activation pathways and especially in the amplification loop of complement activation (Table R.3.7). Table R.3.7: IFN-γ influence on gene expression of complement components in BMM of BALB/c and C57BL/6 mice. Rosetta Resolver Annotation fold change a strain difference gene Entrez description alias name Gene ID BALB/c C57BL/6 control IFN-γ C1qa complement component 1, q subcomponent, alpha polypeptide C1q 12259 1.3 2.3 C1qb complement component 1, q subcomponent, beta polypeptide 12260 2.2 2.8 x x C1qc complement component 1, q subcomponent, C chain C1qg, Ciqc 12262 1.6 2.8 x C1r complement component 1, r subcomponent C1ra, C1rb 50909 4.3 4.7 C1rb complement component 1, r subcomponent, b 270510 5.5 6.3 C3 complement component 3 ASP, Plp 12266 4.9 5.6 Cfb complement factor B B, Bf, Fb, H2-Bf 14962 14.1 19.5 a Fold change values were calculated from expression intensities of IFN-γ treated BMM in comparison to control BMM from the mean of three biological replicates. Differential expression in statistical testing with p* < 0.01 and a minimal absolute fold change of 1.5 is indicated in bold. Other immune function related gene expression changes were conspicuous in BMM after IFN-γ treatment. Inducible nitric oxide synthase 2 (Nos2) was increased as expected in treated BMM. The enzyme produces NO, which acts as antimicrobial effector and as signal mediator during immune defense processes. Another induced enzyme gene was kynureninase (Lkynurenine hydrolase, Kynu) whose product is involved in the degradation of kynurenines, toxic intermediates with signaling properties. Their production is amplified in inflammation settings by the induction of indoleamine 2,3-dioxygenase (IDO), which catalyzes the first step of tryptophan degradation in the kyurenine pathway. Interestingly, the Ido gene was not differentially expressed in BMM after IFN-γ treatment, expression was even absent in the majority of samples. The tryptophanyl-tRNA synthetase (Wars) was induced in IFN-γ treated BMM. Prostaglandin- 101
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G E N O M E W I D E C H A R A C T E
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Maren Depke C O N T E N T S GENOMEW
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Maren Depke Z U S A M M E N F A S S
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Maren Depke Zusammenfassung der Dis
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Maren Depke S U M M A R Y O F D I S
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Maren Depke Summary of Dissertation
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Maren Depke I N T R O D U C T I O N
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Maren Depke Introduction Besides op
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Maren Depke Introduction Extracellu
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Maren Depke Introduction 2005). SaP
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Maren Depke Introduction contains a
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Maren Depke Introduction via fibron
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Maren Depke Introduction cathelicid
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Maren Depke Introduction shock are
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Maren Depke Introduction STUDIES OF
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Maren Depke Introduction are effect
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Maren Depke Introduction cell stimu
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Maren Depke Introduction channel CF
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Maren Depke M A T E R I A L A N D M
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Maren Depke Material and Methods Li
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Maren Depke D I S C U S S I O N A N
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Maren Depke Discussion and Conclusi
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Maren Depke References Athanasopoul
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Maren Depke References Byrne GI, Le
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Maren Depke References Demling R. T
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Maren Depke References Foss GS, Pry
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Maren Depke References Hagopian K,
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Maren Depke References Jin T, Bokar
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Maren Depke References Kwan T, Liu
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Maren Depke References Luster AD, U
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Maren Depke References Puccetti P.
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Maren Depke References Siewert E, B
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Maren Depke References Yang XL, Sch
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Maren Depke A F F I D A V I T / E R
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Maren Depke Acknowledgments Kidney
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