東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Liver-Dependent Protection during Pn...

Kim, Yuri.

Linked to FindBook

Google Book

Amazon

博客來

Liver-Dependent Protection during Pneumonia and Sepsis.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Liver-Dependent Protection during Pneumonia and Sepsis./
Author:	Kim, Yuri.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	148 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-12, Section: B.
Contained By:	Dissertations Abstracts International80-12B.
Subject:	Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13814485
ISBN:	9781392295960

Liver-Dependent Protection during Pneumonia and Sepsis.
Kim, Yuri.

Liver-Dependent Protection during Pneumonia and Sepsis. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 148 p.

Source: Dissertations Abstracts International, Volume: 80-12, Section: B.

Thesis (Ph.D.)--Boston University, 2019.

This item must not be sold to any third party vendors.

Pneumonia and sepsis are distinct but linked public health concerns. Each condition is the leading cause of the other; however, the responses controlling the susceptibility between the two disease processes remain speculative. The acute phase response (APR) is an important component of the host immune response during pneumonia and sepsis, and primarily driven by the activation of hepatocyte transcription factors NF-κB RelA and STAT3.While the NF-κB pathway is essential for inflammation and hepatocyte function, its inactivation has been associated with hepatotoxicity. Liver injury is an independent risk factor for sepsis morbidity and mortality, suggesting that pathways promoting liver homeostasis may limit the systemic consequences of pneumonia. To identify conditions in which NF-κB RelA is required for liver resilience, we challenged mice lacking hepatocyte RelA (hepRelAΔ/Δ) and wildtype (WT) controls with E. coli, K. pneumoniae, S. pneumoniae, LPS, or αGalCer to induce pneumonia, sepsis, and/or NKT cell activation. Severe hepatotoxicity was observed in hepRelAΔ/Δ mice in all conditions examined in association with apoptosis, which could be prevented by neutralization of TNFα. Lastly, these changes were associated with remodeling of the hepatic transcriptome, likely reflecting both the cause and consequence of hepatoxicity.We have previously shown that activation of STAT3 in hepatocytes limits pneumonia susceptibility during endotoxemia, but the mechanisms whereby this liver APR provides protection are unknown. Iron sequestration is a defense mechanism against bacterial infections, which require iron for growth. Based on previous observations that alveolar lining fluid is favorable for bacteria in the absence of liver STAT3, we investigated whether liver APR limits pneumonia susceptibility during sepsis by withholding iron to prevent bacterial outgrowth. WT mice or mice lacking hepatocyte STAT3 (hepSTAT3Δ/Δ) mice were challenged with endotoxemia followed by E. coli pneumonia, or cecal ligation and puncture (CLP). Induction of mRNA encoding several essential iron-regulating factors was ablated in hepSTAT3Δ/Δ mice after endotoxemia and pneumonia, and post CLP. Additionally, liver STAT3 activation significantly remodeled the pulmonary transcriptome during endotoxemia, which potentially represents other protective mechanisms.Taken together, these results suggest that hepatic APR is an important immunological interface modulating pneumonia and sepsis interaction and susceptibility.

ISBN: 9781392295960Subjects--Topical Terms:

611031
Immunology.
Subjects--Index Terms:

Acute phase response

Liver-Dependent Protection during Pneumonia and Sepsis.
LDR:03666nmm a2200361 4500 001 2272437
005 20201105110055.5
008 220629s2019 ||||||||||||||||| ||eng d
020 $a 9781392295960
035 $a (MiAaPQ)AAI13814485
035 $a (MiAaPQ)bu:14489
035 $a AAI13814485
040 $a MiAaPQ $c MiAaPQ
100 1 $a Kim, Yuri. $3 1905081
245 1 0 $a Liver-Dependent Protection during Pneumonia and Sepsis.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 148 p.
500 $a Source: Dissertations Abstracts International, Volume: 80-12, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Quinton, Lee J.
502 $a Thesis (Ph.D.)--Boston University, 2019.
506 $a This item must not be sold to any third party vendors.
520 $a Pneumonia and sepsis are distinct but linked public health concerns. Each condition is the leading cause of the other; however, the responses controlling the susceptibility between the two disease processes remain speculative. The acute phase response (APR) is an important component of the host immune response during pneumonia and sepsis, and primarily driven by the activation of hepatocyte transcription factors NF-κB RelA and STAT3.While the NF-κB pathway is essential for inflammation and hepatocyte function, its inactivation has been associated with hepatotoxicity. Liver injury is an independent risk factor for sepsis morbidity and mortality, suggesting that pathways promoting liver homeostasis may limit the systemic consequences of pneumonia. To identify conditions in which NF-κB RelA is required for liver resilience, we challenged mice lacking hepatocyte RelA (hepRelAΔ/Δ) and wildtype (WT) controls with E. coli, K. pneumoniae, S. pneumoniae, LPS, or αGalCer to induce pneumonia, sepsis, and/or NKT cell activation. Severe hepatotoxicity was observed in hepRelAΔ/Δ mice in all conditions examined in association with apoptosis, which could be prevented by neutralization of TNFα. Lastly, these changes were associated with remodeling of the hepatic transcriptome, likely reflecting both the cause and consequence of hepatoxicity.We have previously shown that activation of STAT3 in hepatocytes limits pneumonia susceptibility during endotoxemia, but the mechanisms whereby this liver APR provides protection are unknown. Iron sequestration is a defense mechanism against bacterial infections, which require iron for growth. Based on previous observations that alveolar lining fluid is favorable for bacteria in the absence of liver STAT3, we investigated whether liver APR limits pneumonia susceptibility during sepsis by withholding iron to prevent bacterial outgrowth. WT mice or mice lacking hepatocyte STAT3 (hepSTAT3Δ/Δ) mice were challenged with endotoxemia followed by E. coli pneumonia, or cecal ligation and puncture (CLP). Induction of mRNA encoding several essential iron-regulating factors was ablated in hepSTAT3Δ/Δ mice after endotoxemia and pneumonia, and post CLP. Additionally, liver STAT3 activation significantly remodeled the pulmonary transcriptome during endotoxemia, which potentially represents other protective mechanisms.Taken together, these results suggest that hepatic APR is an important immunological interface modulating pneumonia and sepsis interaction and susceptibility.
590 $a School code: 0017.
650 4 $a Immunology. $3 611031
653 $a Acute phase response
653 $a Liver injury
653 $a Pneumonia
653 $a Sepsis
690 $a 0982
710 2 $a Boston University. $b Pathology GMS. $3 3285981
773 0 $t Dissertations Abstracts International $g 80-12B.
790 $a 0017
791 $a Ph.D.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13814485