Pro-inflammatory cytokine expression through NF-kappaB/IkappaB pathway in lung epithelial cells.
10.4046/trd.2000.49.3.332
- Author:
Gye Young PARK
;
Seung Hee LEE
;
Bin HWANGBO
;
Jae Joon YIM
;
Choon Taek LEE
;
Young Whan KIM
;
Sung Koo HAN
;
Young Soo SHIM
;
Chul Gyu YOO
- Publication Type:Original Article
- Keywords:
NF-κB;
IκBα;
Lung epithelial cells;
Pro-inflammatory cytokine
- MeSH:
Blotting, Northern;
Blotting, Western;
Cytokines;
Epithelial Cells*;
Inflammation;
Interleukin-8;
Lung Diseases;
Lung*;
Phosphorylation;
Proteasome Inhibitors;
RNA, Messenger;
Signal Transduction;
Tumor Necrosis Factor-alpha
- From:Tuberculosis and Respiratory Diseases
2000;49(3):332-342
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: The importance of pro-inflammatory cytokines, especially tumor necrosis factor α(TNF-α) and interleukin-1β(IL-1β), have been extensively documented in the generation of inflammatory lung disease. Lung epithelial cells are also actively involved in initiating and maintaining inflammation by producing pro-inflammatory mediators. Understanding the mechanism of pro-inflammatory cytokine expression in lung epithelial cells is crucial to the development of new therapeutic modalities for inflammatory lung disease. Transcription of most pro-inflammatory cytokines is dependent on the actiation of NF-κB. However, the relationship between pro-inflammatory cytokine expression and NF-κB/IκB pathway in lung epithelial cells is not clear. METHODS: BEAS-2B, A549, NCI-H719 cells were stimulated with IL-1β or TNF-α at various times, and then IL-8 and TNF-αmRNA expressions were assayed by Northern blot analysis. IL-1β or TNF-α-induced NF-κB activation was assessed by the nuclear translocation of p65 NF-κB subunit. The degradation of IκBα and IκBβ by IL-1βor TNF-α stimulation was assayed by Western blot analysis. The phosphorylation of IκBαwas evaluated by Western blot analysis after pre-treating cells with proteasome inhibitor followed by IL-1β or TNF-α stimulation. The basal level of IKKα expression was evaluated by Western blot analysis. RESULTS: IκBαand IκBβ was repidly degraded after 5 minutes of incubation with IL-1β or TNF-α in BEAS-2B, A549, and NCI-H157 cells. The activation of NF-κB and the induction of IL-8 and TNF-α mRNA expressions were observed by IL-1β or TNF-α stimulation in these cells. In contrast, neither the changes in NF-κB/IκB pathway nor IL-8 and TNF-α mRNA expression was induces by IL-1β or TNF-α stimulation in NCI-H719 cell. IL-1β and TNF-α-induced IκB phoshorylation was observed in BEAS-2B, A549, and NCI-H157 cells, but not in NCI-H719 cells. The basal level of IKKα expression was not different between cells. CONCLUSION: NF-κB/IκB pathway plays an important role in the ixpression of pro-inflammatory cytokine in most lung epithelial cells. The absence of the effect on NF-κB/IκB pathway in NCI-H719 cells seems to be due to the defect in the intracellular signal transduction pathway upstream to IKK.
