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EOH Journal Club

EOH Journal Club - Spring 2017 - Heng Bai

Thursday 3/23 11:00AM - 12:00PM
Bridgeside Point - 339
EOH Journal Club Seminar - Spring 2017

Date: Thursday March 23, 2017
Time: 11am - 12pm
Presenter: Heng Bai

In vivo activation of a T helper 2-driven innate immune response in
lung fibrosis induced by multi-walled carbon nanotubes

Authors: Dong J, Ma Q

Pulmonary exposure to certain forms of carbon nanotubes (CNT) induces
fibrosing lesions in the lungs that manifest an acute inflammation
followed by chronic interstitial fibrosis. The mechanism of CNT-induced
fibrogenesis is largely unknown. The biphasic development with
drastically distinct pathologic manifestations suggests a junction of
acute-to-chronic transition. Here we analyzed the molecular pathways and
regulators underlying the pathologic development of CNT-induced lung
fibrosis. Mice were exposed to multi-walled CNT (MWCNT; XNRI MWNT-7,
Mitsui; 40 μg) by pharyngeal aspiration for 7 days along with vehicle
and carbonaceous controls. Genome-wide microarray analyses of the lungs
identified a range of differentially expressed genes that potentially
function in the acute-to-chronic transition through pathways involving
immune and inflammatory regulation, responses to stress and
extracellular stimuli, and cell migration and adhesion. In particular, a
T helper 2 (Th2)-driven innate immune response was significantly
enriched. We then demonstrated that MWCNT induced the expression of Th2
cytokines interleukin (IL)-4 and IL-13, and a panel of signature
downstream genes, such as Il4i1, Chia, and Ccl11/Eotaxin, time
dependently. Induction of Th2 cytokines took place in CD4+ T lymphocytes
indicating activation of Th2 cells. Furthermore, induction involved
activation of a Th2 cell-specific signaling pathway through
phosphorylation of STAT6 and up-regulation of GATA-3 to mediate the
transcription of Th2 target genes. Our study uncovers activation of a
Th2-driven immune/inflammatory response during pulmonary fibrosis
development induced by MWCNT. The findings provide novel insights into
the molecular events that control the transition from an acute
inflammatory response to chronic fibrosis through Th2 functions in
CNT-exposed lungs

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Last Updated On Friday, February 24, 2017 by Orbell, Adam W
Created On Friday, February 24, 2017

© 2017 by University of Pittsburgh Graduate School of Public Health

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