Abundant TNF-LIGHT expression in the airways of patients with asthma with persistent airflow limitation: Association with nitrative and inflammatory profiles

Tsunahiko Hirano; Kazuto Matsunaga; Keiji Oishi; Keiko Doi; Misa Harada; Junki Suizu; Keita Murakawa; Ayumi Chikumoto; Yuichi Ohteru; Kazuki Matsuda; Sho Uehara; Kazuki Hamada; Shuichiro Ohata; Yoriyuki Murata; Yoshikazu Yamaji; Maki Asami-Noyama; Nobutaka Edakuni

doi:10.1016/j.resinv.2021.05.011

Abundant TNF-LIGHT expression in the airways of patients with asthma with persistent airflow limitation: Association with nitrative and inflammatory profiles

Respir Investig. 2021 Sep;59(5):651-660. doi: 10.1016/j.resinv.2021.05.011. Epub 2021 Jul 7.

Authors

Tsunahiko Hirano¹, Kazuto Matsunaga², Keiji Oishi³, Keiko Doi², Misa Harada², Junki Suizu², Keita Murakawa², Ayumi Chikumoto², Yuichi Ohteru², Kazuki Matsuda², Sho Uehara², Kazuki Hamada², Shuichiro Ohata², Yoriyuki Murata³, Yoshikazu Yamaji², Maki Asami-Noyama², Nobutaka Edakuni²

Affiliations

¹ Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, 755-8505, Japan. Electronic address: tsuna@yamaguchi-u.ac.jp.
² Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, 755-8505, Japan.
³ Department of Medicine and Clinical Science, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, 755-8505, Japan.

PMID: 34244107
DOI: 10.1016/j.resinv.2021.05.011

Abstract

Background: The role of the inflammatory secretory protein TNF-LIGHT (LIGHT) in the molecular mechanisms underlying persistent airflow limitation (PAL) in asthma remains unclear. We hypothesized that high airway LIGHT expression may be a feature of asthma with PAL associated with specific expression patterns of inflammatory molecules.

Methods: This hypothesis was tested in 16 patients with asthma on inhaled corticosteroid treatment. Induced sputum was collected, the expression of LIGHT and 3-nitrotyrosine (NT), which reflects the footprint of reactive nitrogen species content, was measured using immunohistochemical staining, and the inflammatory molecules in the sputum supernatant were analyzed using a magnetic bead array.

Results: LIGHT staining in the cells had a significantly higher intensity in participants with PAL than in participants without PAL (47.9 × 10⁴/ml vs. 5.4 × 10⁴/ml; p < 0.05). The array analysis indicated that IL-8, IL-19, matrix metalloproteinase 2, and osteopontin, were associated with high LIGHT immunoreactivity. The fractionation of 3-NT-positive cells was positively correlated with that of LIGHT-positive cells (r = 0.57, p < 0.05) and the TGF-β1 level (r = 0.61, p < 0.05). LIGHT- and 3-NT-positive cells showed significant positive correlation with the differential cell counts of neutrophils, macrophages, and eosinophils in the induced sputum. Intense immunoreactivities of LIGHT (r = -0.54, p < 0.05) and 3-NT (r = -0.42, p = 0.1) were negatively associated with decreased forced expiratory volume in 1/forced vital capacity ratio.

Conclusions: The findings suggest that LIGHT is a key component in the association between airway inflammation and airflow limitation in patients with asthma, and its expression may be persistently correlated with the abundance of inflammatory cells and inflammatory and profibrogenic radical/molecules.

Keywords: Airway remodeling; Asthma; Inflammatory mediator; LIGHT; Nitrative stress.

MeSH terms

Asthma* / metabolism
Eosinophils
Forced Expiratory Volume
Humans
Matrix Metalloproteinase 2* / metabolism
Respiratory System
Sputum
Tumor Necrosis Factor Ligand Superfamily Member 14

Substances

TNFSF14 protein, human
Tumor Necrosis Factor Ligand Superfamily Member 14
Matrix Metalloproteinase 2