Abstract
Background The COP9 signalosome (CSN) is a highly conserved
protein complex composed of eight subunits. The individual CSN subunits
play essential roles in cell proliferation, signal transduction
modulation, gene transcription, angiogenesis, and microenvironmental
homeostasis. However, the exact role of CSN subunit 5 (CSN5) in
bronchial asthma remains unclear. Methods The potential link
between CSN5 and bronchial asthma was investigated in ovalbumin
(OVA)-induced asthma in mice. Samples from HMVEC-L cells treated with
Dermatophagoides pteronyssinus (Derp1) and CSN5 small interfering RNA
were collected to determine the expression of NF-κB, IκBα, IKKβ, PD-L1,
and CSN5. Furthermore, plasma CSN5 levels in asthma patients (stable and
exacerbated states) were analyzed. Results Plasma CSN5 levels
were higher in patients with exacerbated asthma (n = 19) than in healthy
controls (n = 10) or patients with stable asthma (n = 10). The CSN5
level was correlated with lung function in patients with asthma. CSN5
silencing in HMVEC-L cells reduced the NF-κB protein level at 4 h and
PD-L1 level at 4 h, 8 h, and 24 h after Derp1 treatment. Goblet
cell hyperplasia, lung fibrosis, and the levels of CSN5, PD-L1, NF-κB,
p-IκBα, p-IKKβ, IL13, and INFγ proteins increased at 33 and 80 days in
OVA-sensitized/challenged mice compared with control mice, but these
changes were reduced by PD-L1 inhibitor treatment. Conclusions
The results indicate that CSN5 interacts with PD-L1 in asthma and may be
a potential target for asthma treatment.