IL-13 in LPS-Induced Inflammation Causes Bcl-2 Expression to Sustain Hyperplastic Mucous cells

Chand, Hitendra S.; Harris, Jennifer F.; Tesfaigzi, Yohannes

doi:10.1038/s41598-017-18884-9

IL-13 in LPS-Induced Inflammation Causes Bcl-2 Expression to Sustain Hyperplastic Mucous cells

Journal Article · Thu Jan 11 00:00:00 EST 2018 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-017-18884-9· OSTI ID:1624375

^[1]; Harris, Jennifer F. ^[2]; Tesfaigzi, Yohannes ^[3]

Florida International University, Miami, FL, (United States). Department of Immunology, Herbert Wertheim College of Medicine; COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM, (United States); DOE/OSTI
COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM (United States); Los Alamos National Lab (LANL), Los Alamos, NM (United States). Bioscience Division
COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM (United States)

Exposure to lipopolysaccharides (LPS) causes extensive neutrophilic inflammation in the airways followed by mucous cell hyperplasia (MCH) that is sustained by the anti-apoptotic protein, Bcl-2. To identify inflammatory factor(s) that are responsible for Bcl-2 expression, we established an organ culture system consisting of airway epithelial tissue from the rat nasal midseptum. The highest Muc5AC and Bcl-2 expression was observed when organ cultures were treated with brochoalveolar lavage (BAL) fluid harvested from rats 10 h post LPS instillation. Further, because BAL harvested from rats depleted of polymorphonuclear cells compared to controls showed increased Bcl-2 expression, analyses of cytokine levels in lavages identified IL-13 as an inducer of Bcl-2 expression. Ectopic IL-13 treatment of differentiated airway epithelial cells increased Bcl-2 and MUC5AC expression in the basal and apical regions of the cells, respectively. When Bcl-2 was blocked using shRNA or a small molecule inhibitor, ABT-263, mucous cell numbers were reduced due to increased apoptosis that disrupted the interaction of Bcl-2 with the pro-apoptotic protein, Bik. Furthermore, intranasal instillation of ABT-263 reduced the LPS-induced MCH in bik ^+/+ but not bik ^-/- mice, suggesting that Bik mediated apoptosis in hyperplastic mucous cells. Therefore, blocking Bcl-2 function could be useful in reducing IL-13 induced mucous hypersecretion.

View Accepted Manuscript (DOE)

Research Organization:: Los Alamos National Lab (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-06NA25396

OSTI ID:: 1624375

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 8; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Bcl-2 Sustains Increased Mucous and Epithelial Cell Numbers in Metaplastic Airway Epithelium J., Fischer, Mark; R., Hotchkiss, Jon; R., Harkema, Jack The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/sa7c-td41	text	January 2005
Chronic Obstructive Pulmonary Disease: An Update on Diagnosis and Management Issues in Older Adults Nazir, Shoab A.; Erbland, Marcia L. Drugs & Aging, Vol. 26, Issue 10 https://doi.org/10.2165/11316760-000000000-00000	journal	January 2009
Epigen is induced during the interleukin-13–stimulated cell proliferation in murine primary airway epithelial cells Taniguchi, Kazuto; Yamamoto, Shuichi; Aoki, Shigehisa Experimental Lung Research, Vol. 37, Issue 8 https://doi.org/10.3109/01902148.2011.596894	journal	August 2011
Intracellular Insulin-like Growth Factor-1 Induces Bcl-2 Expression in Airway Epithelial Cells Chand, Hitendra S.; Harris, Jennifer Foster; Mebratu, Yohannes The Journal of Immunology, Vol. 188, Issue 9 https://doi.org/10.4049/jimmunol.1102673	journal	March 2012
Th2 Cytokine Production from Mast Cells Is Directly Induced by Lipopolysaccharide and Distinctly Regulated by c-Jun N-Terminal Kinase and p38 Pathways Masuda, Akio; Yoshikai, Yasunobu; Aiba, Keiko The Journal of Immunology, Vol. 169, Issue 7 https://doi.org/10.4049/jimmunol.169.7.3801	journal	October 2002
Opposing Actions of Stat1 and Stat6 on IL-13-Induced Up-Regulation of Early Growth Response-1 and Platelet-Derived Growth Factor Ligands in Pulmonary Fibroblasts Ingram, Jennifer L.; Antao-Menezes, Aurita; Mangum, James B. The Journal of Immunology, Vol. 177, Issue 6 https://doi.org/10.4049/jimmunol.177.6.4141	journal	September 2006
Chronic obstructive pulmonary disease Dean, Erin Nursing Standard, Vol. 31, Issue 40 https://doi.org/10.7748/ns.31.40.15.s16	journal	May 2017

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Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration Garcia, Sandra Ruiz; Deprez, Marie; Lebrigand, Kevin https://doi.org/10.1101/451807	posted_content	October 2018
Advanced age protects resistance arteries of mouse skeletal muscle from oxidative stress through attenuating apoptosis induced by hydrogen peroxide Norton, Charles E.; Sinkler, Shenghua Y.; Jacobsen, Nicole L. The Journal of Physiology, Vol. 597, Issue 15 https://doi.org/10.1113/jp278255	journal	July 2019
Pulmonary Neuroendocrine Cells Secrete γ-Aminobutyric Acid to Induce Goblet Cell Hyperplasia in Primate Models Barrios, Juliana; Kho, Alvin T.; Aven, Linh American Journal of Respiratory Cell and Molecular Biology, Vol. 60, Issue 6 https://doi.org/10.1165/rcmb.2018-0179oc	journal	June 2019
Pulmonary neuroendocrine cells secrete γ-aminobutyric acid to induce goblet cell hyperplasia in primate models S. H., Randell,; L. A., Miller,; J. A., Mitchel, American Thoracic Society https://doi.org/10.17615/47ct-w049	text	January 2019

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