| First Author | Long XB | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 4 | Pages | e35960 |
| PubMed ID | 22558282 | Mgi Jnum | J:225006 |
| Mgi Id | MGI:5689958 | Doi | 10.1371/journal.pone.0035960 |
| Citation | Long XB, et al. (2012) Clara cell 10-kDa protein gene transfection inhibits NF-kappaB activity in airway epithelial cells. PLoS One 7(4):e35960 |
| abstractText | BACKGROUND: Clara cell 10-kDa protein (CC10) is a multifunctional protein with anti-inflammatory and immunomodulatory effects. Induction of CC10 expression by gene transfection may possess potential therapeutic effect. Nuclear factor kappaB (NF-kappaB) plays a key role in the inflammatory processes of airway diseases. METHOD/RESULTS: To investigate potential therapeutic effect of CC10 gene transfection in controlling airway inflammation and the underlying intracellular mechanisms, in this study, we constructed CC10 plasmid and transfected it into bronchial epithelial cell line BEAS-2B cells and CC10 knockout mice. In BEAS-2B cells, CC10's effect on interleukin (IL)-1beta induced IL-8 expression was explored by means of RT-PCR and ELISA and its effect on NF-kappaB classical signaling pathway was studied by luciferase reporter, western blot, and immunoprecipitation assay. The effect of endogenous CC10 on IL-1beta evoked IL-8 expression was studied by means of nasal explant culture. In mice, CC10's effect on IL-1beta induced IL-8 and nuclear p65 expression was examined by immunohistochemistry. First, we found that the CC10 gene transfer could inhibit IL-1beta induced IL-8 expression in BEAS-2B cells. Furthermore, we found that CC10 repressed IL-1beta induced NF-kappaB activation by inhibiting the phosphorylation of IkappaB-alpha but not IkappaB kinase-alpha/beta in BEAS-2B cells. Nevertheless, we did not observe a direct interaction between CC10 and p65 subunit in BEAS-2B cells. In nasal explant culture, we found that IL-1beta induced IL-8 expression was inversely correlated with CC10 levels in human sinonasal mucosa. In vivo study revealed that CC10 gene transfer could attenuate the increase of IL-8 and nuclear p65 staining in nasal epithelial cells in CC10 knockout mice evoked by IL-1beta administration. CONCLUSION: These results indicate that CC10 gene transfer may inhibit airway inflammation through suppressing the activation of NF-kappaB, which may provide us a new consideration in the therapy of airway inflammation. |
