폐 상피세포에서 Rhinovirus에 의한 RANTES의 생성 기전The Mechanism of RANTES Production by Rhinovirus in Alveolar Epithelial Cells: Evidence for NF-κB-dependent Transcriptional Activation
- Other Titles
- The Mechanism of RANTES Production by Rhinovirus in Alveolar Epithelial Cells: Evidence for NF-κB-dependent Transcriptional Activation
- Authors
- 신성준; 김상헌; 김태형; 손장원; 윤호주; 신동호; 박성수
- Issue Date
- Feb-2006
- Publisher
- 대한천식알레르기학회
- Keywords
- Rhinovirus; RANTES; Nuclear-factor kappa B; A549 cell
- Citation
- 천식 및 알레르기, v.26, no.1, pp.19 - 26
- Indexed
- KCI
- Journal Title
- 천식 및 알레르기
- Volume
- 26
- Number
- 1
- Start Page
- 19
- End Page
- 26
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/181740
- ISSN
- 1226-8739
- Abstract
- Background: Rhinovirus (RV) is a well-known cause of upper respiratory tract infections and an important trigger of asthmatic exacerbation. RV can augment tissue eosino philia when combined with antigen in appropriately sensi. tized patients. RANTES, a subfamily of chemokines with double cysteine motif, is a potent eosinophil chemoattractant. Objective: This study was designed to investigate RV stim ulation of RANTES and NF-kB-dependent transcriptional mechanism in alveolar epithelial cells in vitro. Method: After RV14 infecion on A549 cells, RANTES protein and mRNA were measured using ELISA and RTPCR. To further understand the transcriptional mechanisms of RANTES production, NF-kB activity was checked with gel shift assay including supershift and competition assay. The mechanism of RANTES promoter activation was analyzed by cis-element assay with mutagenesis experiment. NF-KB activity was inhibited with antioxidant, TLCK, TPCK, and mutant I KB a Result: RANTES and mRNA levels were increased and
peaked at 12 hours after infection with RV14. RV also stimulated NF-KB-DNA binding activity. Supershift assays revealed that this binding was due to p65 and, to a lesser extent, p50 NF-kB subunits. Cis-element analysis of RANTES promoter showed that NF-kB binding site between -50 and -40 was the most important region. A dominant negative mutant of IxBa abrogated RV-induced RANTES promoter activity. Selective antioxidants, N-acetylcysteine, and NF-K B blockers (TLCK, TPCK) inhibited RV-stimulated RANTES production and promoter activity in alveolar epithelial cells. Conclusion: RV is a potent stimulator of RANTES production in A549 cells in vitro. This inductive effect is, to a great extent, transcriptionally mediated and dependent on NF-kB activation. The most important subuinits of NF-KB are p65/p50, which are interacted with RNATES promoter site between -50 and -40. RANTES production, are inhibited by antioxidant and NF-kB blockers.
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