Abundant TNF-LIGHT expression in the airways of patients with asthma with persistent airflow limitation: Association with nitrative and inflammatory profiles |
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| Affiliation: | 1. Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, 755-8505, Japan;2. Department of Medicine and Clinical Science, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, 755-8505, Japan;1. Department of Respiratory Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan;2. Department of Microbiology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan;3. Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan;1. Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan;2. Kinki Hokuriku Airway Disease Conference, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan;3. NPO Sapporo Cough Asthma and Allergy Center, Minami 4-jo Nishi 15-chome, Chuo-ku, Sapporo, 064-0804, Japan;4. Hiroshima Allergy and Respiratory Clinic, 14-7 Hatchobori, Naka-ku, Hiroshima, 730-0013, Japan;1. Pneumologia, Ospedale Misericordia, Grosseto, Italy;2. Istituto di Fisiologia Clinica, CNR, Pisa, Italy;3. Cardio Thoracic and Vascular Department, Pathophysiology Unit, University of Pisa, Italy;4. DIMPEFINU, Unit of Pneumology and Medicine, University of Palermo, Palermo, Italy;5. Pneumologia, Ospedale S.Corona, Pietra Ligure, Italy;1. Department of Respiratory Medicine, Nara Medical University, 840 Shijo-cho, Kashihara-city, Nara, 634-8522, Japan;2. Department of Respiratory Medicine, Minami-Nara General Medical Center, 8-1 Fukugami, Oyodo-cho, Yoshino-gun, Nara, 638-8551, Japan;3. TME Therapeutics Inc., 2-16-1 Higashi-shinbashi, Minato-ku, Tokyo, 105-0021, Japan;4. Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose-city, Tokyo, 204-8522, Japan;1. UMDNJ-NJ Medical School, Cedar Knolls, New Jersey;2. Northwestern University, Chicago, Illinois |
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| Abstract: | BackgroundThe 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.MethodsThis 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.ResultsLIGHT 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.ConclusionsThe 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. |
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| Keywords: | Asthma Airway remodeling LIGHT Nitrative stress Inflammatory mediator ACQ" },{" #name" :" keyword" ," $" :{" id" :" kwrd0040" }," $$" :[{" #name" :" text" ," _" :" Asthma Control Questionnaire score ECM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0050" }," $$" :[{" #name" :" text" ," _" :" extracellular matrix %FEV1" },{" #name" :" keyword" ," $" :{" id" :" kwrd0060" }," $$" :[{" #name" :" text" ," _" :" percent predicted values of FEV1 FVC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0070" }," $$" :[{" #name" :" text" ," _" :" forced vital capacity HDAC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0080" }," $$" :[{" #name" :" text" ," _" :" histone deacetylase LIGHT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0090" }," $$" :[{" #name" :" text" ," _" :" lymphotoxin-like, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes NF-κB" },{" #name" :" keyword" ," $" :{" id" :" kwrd0100" }," $$" :[{" #name" :" text" ," _" :" nuclear factor kappa B NT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0110" }," $$" :[{" #name" :" text" ," _" :" nitrotyrosine OPN" },{" #name" :" keyword" ," $" :{" id" :" kwrd0120" }," $$" :[{" #name" :" text" ," _" :" osteopontin RNS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0130" }," $$" :[{" #name" :" text" ," _" :" reactive nitrogen species RV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0140" }," $$" :[{" #name" :" text" ," _" :" rhinovirus TGF" },{" #name" :" keyword" ," $" :{" id" :" kwrd0150" }," $$" :[{" #name" :" text" ," _" :" transforming growth factor PAL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0160" }," $$" :[{" #name" :" text" ," _" :" persistent airflow limitation WBC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0170" }," $$" :[{" #name" :" text" ," _" :" white blood cell |
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