Print Email Facebook Twitter Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm Title Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm Author Lindeman, J.H.N. Abdul-Hussien, H. Schaapherder, A.F.M. van Bockel, J.H. von der Thüsen, J.H. Roelen, D.L. Kleemann, R. Publication year 2008 Abstract Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic aneurysm); however, the nature of the inflammatory factors and cellular response(s) involved in AAA growth is controversial. In the present study, we set out to determine the aortic levels of inflammatory cytokines in relation to downstream inflammatory transcription factors and cellular responses. A comparison of AAA wall samples with atherosclerotic wall samples taken from the same aortic region allowed AAA-specific inflammatory parameters to be identified that distinguish AAAs from ASD (aortic atherosclerotic disease). RT-PCR (real-time PCR), ELISA, Western blotting and immunohistochemistry were combined to assess cytokines and transcription factors at the mRNA and protein level, and their activation status. Compared with ASD, inflammatory parameters associated with Th1-type [T-bet, IL (interleukin)-2, IFN-γ (interferon-γ), TNF-α (tumour necrosis factor-α), IL-1α and cytotoxic T-cells] and Th2-type [GATA3, IL-4, IL-10, IL-13 and B-cells] responses were all increased in AAA samples. Evaluation of major downstream inflammatory transcription factors revealed higher baseline levels of C/EBP (CCAAT/enhancer-binding protein) α;, β and δ in the AAA samples. Baseline p65 NF-κB (nuclear factor κB) and c-Jun [AP-1 (activator protein-1)] levels were comparable, but their activated forms were strongly increased in the AAA samples. Downstream target genes of p65 NF-κB, c-Jun, IL-6 and IL-8 were hyperexpressed. Molecular and cellular processes associated with IL-6 and IL-8 hyperactivation were enhanced in the AAA samples, i.e. the expression of phospho-STAT-3 (signal transducer and activator of transcription-3) and perforin were elevated, and the content of plasma cells, neutrophils and vasa vasorum was increased. In conclusion, our findings demonstrate that an AAA is a general inflammatory condition which is characterized by enhanced expression and activation of pro-inflammatory transcription factors, accompanied by IL-6 and IL-8 hyperexpression and exaggerated downstream cellular responses, which together clearly distinguish an AAA from ASD. © The Authors. Chemicals / CAS: gamma interferon, 82115-62-6; interleukin 13, 148157-34-0; interleukin 2, 85898-30-2; interleukin 8, 114308-91-7; perforin, 119332-27-3; transcription factor GATA 3, 137878-55-8; Biological Markers; Inflammation Mediators; Interleukin-6; Interleukin-8; Transcription Factors Subject HealthAbdominal aortic aneurysmAtherosclerosisInflammationInterleukinTranscription factorCCAAT enhancer binding protein alphaCCAAT enhancer binding protein betaCCAAT enhancer binding protein deltaCytokineGamma interferonInterleukin 10Interleukin 13Interleukin 1alphaInterleukin 2Interleukin 4Interleukin 6Interleukin 8Messenger RNAPerforinSTAT3 proteintranscription factortranscription factor AP 1transcription factor GATA 3transcription factor RelAtranscription factor T bettumor necrosis factor alphaautacoidbiological markerabdominal aorta aneurysmadultagedaorta atherosclerosisaorta wallB lymphocyteCellular immunityClinical articleControlled studyCytotoxic T lymphocyteEnzyme linked immunosorbent assayFemaleHumanHuman tissueImmunohistochemistryMaleMedical parametersNeutrophilPlasma cellProtein expressionReal time polymerase chain reactionTh1 cellTh2 cellVasa vasorumWestern blottingAorta valve stenosisBiosynthesisDifferential diagnosisGeneticsImmunologyMetabolismMethodologyPhysiologyReverse transcription polymerase chain reactionAgedAortic Aneurysm, AbdominalAortic Valve StenosisAtherosclerosisBiological MarkersDiagnosis, DifferentialFemaleGene Expression ProfilingHumansInflammation MediatorsMaleMiddle AgedReverse Transcriptase Polymerase Chain ReactionTh1 CellsTh2 CellsTranscription Factors To reference this document use: http://resolver.tudelft.nl/uuid:67b23360-115d-4bc4-ad5e-1cfa363d3ecb DOI https://doi.org/10.1042/cs20070352 TNO identifier 240842 ISSN 0143-5221 Source Clinical Science, 114 (11-12), 687-697 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.