Page 23 - H. Cell signaling

Protein acetylation-dependent pathological macrophage activation
drives fine particulate matter-induced chronic obstructive pulmonary disease

Myungkyung Noh , Jeong Yeon Sim , and Ho-Young Lee 1*
1,#
1,#
1 College of Pharmacy, Seoul National University, Seoul, 08826, Korea
Background Aim

• Particulate matter (PM) has been consistently linked to morbidity • To investigate the mechanism of PM-induced COPD
and mortality from chronic obstructive pulmonary disease (COPD) pathogenesis.
and reduced life expectancy in epidemiological studies. • To discover a potential therapeutic strategy targeting
• The precise mechanisms by which PM exposure induces the central pathway of PM-driven COPD.
development of COPD remain elusive.

Method

• Establishment of PM-induced COPD mouse model
• Hematoxylin&Eosin, Masson’s trichrome, Periodic
PBS
Control Intratracheal injection acid-Schiff staining
• Flow cytometry for infiltrated immune cells in the lung
PM • Immunofluorescence staining
PM Intratracheal injection • RNA-sequencing, Gene ontology (GO) analysis
Lung function test Histological
analysis

Results

1. Chronic PM exposure results in 2. Inflammatory macrophages 3. Post-translational protein acetylation is one of
severe COPD in mice. were the primary mediator of the most upregulated gene signature in PM-
PM-induced COPD exposed lung tissue, which drives
Control PM progression. pathological macrophage activation.
* RNA-seq * DAVID GO analysis
Control PM
4.72 % 41.15 %
CD11c-PE

Control PM GO:0034421
post-translational
protein acetylation
CD11b-APC * Gated on F4/80+ population
H&E Control PM Control PM
DAPI/F4/80 DAPI/AcK/CD68

Masson’s trichrome 4. EM-Gp, potential therapeutic agent that targets regulators of protein acetylation,

successfully alleviated PM-induced COPD.
Ers
45 PM PM+EM-Gp
** ** Control PM PM+EM-Gp
40
PM
cmH2O/mL 30 25 DAPI/AcK/CD68
PAS 35 PM+EM-Gp
20
0
Conclusion References Acknowledgements
• Inflammatory macrophages play a • Vlahos, Ross, and Steven Bozinovski. This work was supported by a grant from the
major role in PM-induced COPD "Role of alveolar macrophages in chronic National Research Foundation of Korea (NRF),
pathogenesis. obstructive pulmonary disease." Frontiers the Ministry of Science and ICT (MSIT),
Republic of Korea
• Elevated protein acetylation drives • in immunology 5 (2014): 435. (No. NRF-2016R1A3B1908631).
Ito, Kazuhiro, et al. "Decreased histone
pathological reprogramming of deacetylase activity in chronic obstructive
macrophages. pulmonary disease." New England Journal Contact information
• Targeting protein acetylation with EM- of Medicine 352.19 (2005): 1967-1976.
Gp can be a powerful strategy for PM- Myungkyung Noh
induced COPD treatment. E-mail: monophobian@snu.ac.kr