Dallo, Rossella
(2018)
Relation between Aryl Hydrocarbon Receptor and Interleukin-6 in a human breast cell model and in the Cyp1a1/1a2/1b1(-/-) triple-knockout mouse model, [Dissertation thesis], Alma Mater Studiorum Università di Bologna.
Dottorato di ricerca in
Scienze della terra, della vita e dell'ambiente, 30 Ciclo. DOI 10.6092/unibo/amsdottorato/8664.
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Abstract
This study investigates the relationship between Aryl Hydrocarbon Receptor (AHR) and the pathway of Interleukin-6 (IL6). The physiologic expression of AHR and IL6 is tightly regulated by different mechanisms and dysregulations in the control of their activity have been associated with several adverse outcomes. Here, we analysed their mutual regulation in two different experimental models, a human epithelial breast cell model with an IL6-driven acute inflammation induction and a mouse model triple-knockout for the AHR target genes Cyp1a1/1a2/1b1 (CYP1-KO). Starting from current data demonstrating that AHR mediates the induction of IL6, the aim of this study was: 1) to evaluate if, in our cell model, inflammation driven by IL6 could, in turn, regulate the expression of AHR, and to evaluate whether AHR could assume a role in sustaining inflammation; 2) to investigate whether the CYP1-KO mouse model, which is characterized by a potentiated activation of AHR, presented an induced expression of Il6 or other inflammation-related features, or adverse effects in pathways in which AHR exerts physiological functions. Our results indicate that: i) IL6 administration stimulates STAT3 and AHR expression through the activation of pSTAT3; ii) The induction of endogenous IL6 is regulated by IL6 administration and by AHR activation; iii) IL6 affects cell cycle progression and migration activity; iv) AHR/CYP1 disrupted signaling does not interfere with Il6 expression, but affects Pparγ and Ahr transcription and mammary gland tissue morphology. These results demonstrate that, in MCF10A cell line, AHR could assume an active role in the complex puzzle of early steps of inflammation. In the CYP1-KO we did not identify an altered expression of Il6 indicating that an altered CYP1/AHR signaling does not interfere with IL6-related pathway. However, in contrast, we could observe an altered expression of Pparγ, an important marker in adipogenesis.
Abstract
This study investigates the relationship between Aryl Hydrocarbon Receptor (AHR) and the pathway of Interleukin-6 (IL6). The physiologic expression of AHR and IL6 is tightly regulated by different mechanisms and dysregulations in the control of their activity have been associated with several adverse outcomes. Here, we analysed their mutual regulation in two different experimental models, a human epithelial breast cell model with an IL6-driven acute inflammation induction and a mouse model triple-knockout for the AHR target genes Cyp1a1/1a2/1b1 (CYP1-KO). Starting from current data demonstrating that AHR mediates the induction of IL6, the aim of this study was: 1) to evaluate if, in our cell model, inflammation driven by IL6 could, in turn, regulate the expression of AHR, and to evaluate whether AHR could assume a role in sustaining inflammation; 2) to investigate whether the CYP1-KO mouse model, which is characterized by a potentiated activation of AHR, presented an induced expression of Il6 or other inflammation-related features, or adverse effects in pathways in which AHR exerts physiological functions. Our results indicate that: i) IL6 administration stimulates STAT3 and AHR expression through the activation of pSTAT3; ii) The induction of endogenous IL6 is regulated by IL6 administration and by AHR activation; iii) IL6 affects cell cycle progression and migration activity; iv) AHR/CYP1 disrupted signaling does not interfere with Il6 expression, but affects Pparγ and Ahr transcription and mammary gland tissue morphology. These results demonstrate that, in MCF10A cell line, AHR could assume an active role in the complex puzzle of early steps of inflammation. In the CYP1-KO we did not identify an altered expression of Il6 indicating that an altered CYP1/AHR signaling does not interfere with IL6-related pathway. However, in contrast, we could observe an altered expression of Pparγ, an important marker in adipogenesis.
Tipologia del documento
Tesi di dottorato
Autore
Dallo, Rossella
Supervisore
Dottorato di ricerca
Ciclo
30
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
Aryl Hydrocarbon Receptor, Interleukin-6, Signal Transducer and Activator of Transcription 3
URN:NBN
DOI
10.6092/unibo/amsdottorato/8664
Data di discussione
7 Maggio 2018
URI
Altri metadati
Tipologia del documento
Tesi di dottorato
Autore
Dallo, Rossella
Supervisore
Dottorato di ricerca
Ciclo
30
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
Aryl Hydrocarbon Receptor, Interleukin-6, Signal Transducer and Activator of Transcription 3
URN:NBN
DOI
10.6092/unibo/amsdottorato/8664
Data di discussione
7 Maggio 2018
URI
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