Role of clusterin/progranulin in toluene diisocyanate-induced occupational asthma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-05-01

AUTHORS

Gil-Soon Choi, Hoang Kim Tu Trinh, Eun-Mi Yang, Young-Min Ye, Yoo Seob Shin, Seung-Hyun Kim, Hae-Sim Park

ABSTRACT

Toluene diisocyanate (TDI) exposure induces oxidative stress and epithelial cell-derived inflammation, which affect the pathogenesis of TDI-induced occupational asthma (TDI-OA). Recent studies suggested a role for clusterin (CLU) and progranulin (PGRN) in oxidative stress-mediated airway inflammation. To evaluate CLU and PGRN involvement in airway inflammation in TDI-OA, we measured their serum levels in patients with TDI-OA, asymptomatic exposed controls (AECs), and unexposed healthy normal controls (NCs). Serum CLU and PGRN levels were significantly lower in the TDI-OA group than in the AEC and NC groups (P < 0.05). The sensitivity and specificity for predicting the TDI-OA phenotype were 72.4% and 53.4% when either CLU or PGRN levels were below the cutoff values (≤125 μg/mL and ≤68.4 ng/mL, respectively). If both parameters were below the cutoff levels, the sensitivity and specificity were 58.6% and 89.8%, respectively. To investigate CLU and PGRN function, we evaluated their production by human airway epithelial cells (HAECs) in response to TDI exposure and co-culturing with neutrophils. TDI-human serum albumin stimulation induced significant CLU/PGRN release from HAECs in a dose-dependent manner, which positively correlated with IL-8 and folliculin levels. Co-culturing with neutrophils significantly decreased CLU/PGRN production by HAECs. Intracellular ROS production in epithelial cells co-cultured with neutrophils tended to increase initially, but the ROS production decreased gradually at a higher ratio of neutrophils. Our results suggest that CLU and PGRN may be involved in TDI-OA pathogenesis by protecting against TDI-induced oxidative stress-mediated inflammation. The combined CLU/PGRN serum level may be used as a potential serological marker for identifying patients with TDI-OA among TDI-exposed workers. More... »

PAGES

1-10

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s12276-018-0085-2

DOI

http://dx.doi.org/10.1038/s12276-018-0085-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1103683089

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29717106


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