Recombinant club cell protein 16 (CC16) ameliorates cigarette smoke‑induced lung inflammation in a murine disease model of COPD

Abstract

Club cell protein (CC16) is expressed primarily by club cells possesses anti-inflammatory properties and is located in the bronchiolar epithelium. Previous studies have demonstrated that CC16 deficiency is associated with the progression of chronic obstructive pulmonary disease (COPD). In the present study, the therapeutic effects of recombinant rat CC16 protein in mice with COPD were examined and the underlying mechanisms investigated. A total of 30 adult male C57/BL6 mice were randomly divided into three groups (10 mice/group). A mouse COPD model was generated by exposing 20 mice to cigarette smoke (CS) for 24 weeks. A total of 10 mice were treated intranasally with rCC16 (2.5 µg/g body weight) and control mice were exposed to normal room air. Results indicated that rCC16 treatment ameliorated pathological damage in the lungs and reduced the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8, which were induced by CS exposure. After rCC16 administration, endogenous CC16 was upregulated and the body weight of COPD mice was increased, whereas the opposite was observed in CS-exposed mice. Additionally, rCC16 treatment inhibited the DNA binding of NF-κB/p65 in lung tissues and reduced nuclear translocation of NF-κB/p65 in BALF and epithelial cells. Moreover, rCC16 treatment lead to a decrease in the total number of BALF cells, including macrophages, which was elevated in COPD mice. In conclusion, the present results demonstrate that rCC16 has therapeutic effects on COPD by downregulating pro-inflammatory factors via the NF-κB pathway.

Early local neutralization of CC16 in sepsis‑induced ALI following blunt chest trauma leads to delayed mortality without benefitting overall survival

“…Recently, the anti-inflammatory potential of CC16 24 h post-CLP in this model was confirmed. The local anti-inflammatory characteristic of CC16 is supported by the present data and by results previously demonstrated in non-traumatic lung injury ( 32 , 33 ). A recent study by the authors demonstrated that upon the early intratracheal neutralization of CC16 following chest trauma, reduced lung injury at 24 h post-CLP was observed ( 9 ).…”

Renal dysfunction decreases specificity and overturns cutoff value of serum CC16 while prohibiting 7-day mortality prediction in diagnosing acute respiratory distress syndrome in intensive care unit.

“…Consistent with these studies, Pang demonstrated that recombinant rat CC16 protein inhibits LPS-induced MMP-9 expression and the production of pro-inflammatory cytokines via NF-κB pathway in model of tracheal epithelial cells and RAW264.7 macrophages [25,26]. She suggested that exogenous supplementation of recombinant CC16 ameliorates cigarette smoke-induced lung inflammation in a murine disease model of chronic obstructive pulmonary disease [27]. Further exploration is needed of CC16's function for critical care patients in the future.…”

Triterpene Acids of Loquat Leaf Improve Inflammation in Cigarette Smoking Induced COPD by Regulating AMPK/Nrf2 and NFκB Pathways

“…As part of a family of transcription factors, NFκB increased significantly in CS-induced COPD mice. Therefore, downregulating pro-inflammatory factors via modulation of the NFκB pathway exhibited therapeutic effects on COPD inflammation [38][39][40]. As a pro-inflammatory cytokine, prolonged inducible nitric oxide synthase (iNOS) expression is implicated in the pathophysiology of inflammatory diseases, such as pulmonary inflammation and COPD [41,42].…”