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Role of Rel A and IkappaB of nuclear factor κB in the release of interleukin‐8 by cyclic mechanical strain in human alveolar type II epithelial cells A549
Author(s) -
NING Qiaoming,
WANG Xiangrui
Publication year - 2007
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2007.01166.x
Subject(s) - a549 cell , chromosomal translocation , microbiology and biotechnology , medicine , western blot , messenger rna , secretion , interleukin , lung , andrology , immunology , cytokine , biology , biochemistry , gene
Background and objective: Overdistention of the lung tissue during mechanical ventilation may initiate ventilator‐induced lung injury (VILI). Release of cytokines, including IL‐8, may be responsible for VILI, although the mechanisms remain unclear. This study aimed to determine whether stretch‐induced IL‐8 production is dependent on degradation of IkappaB (IκB) and the resulting Rel A translocation into the nucleus. Methods: A549 cells were exposed to cyclic stretch of varying amplitude, frequency and duration before the mRNA and protein level of IL‐8 were measured. To observe the role of Rel A and IκB of nuclear factor κB, A549 cells were exposed to cyclic stretch for 5 min to 1 h. Real‐time PCR and ELISA respectively were performed to detect mRNA and IL‐8 protein. Rel A and IκBα were assessed by Western blot. Further confirmation was sought using a nuclear factor κB inhibitor (PDTC) before mechanical stretch. Results: A549 cells exposed to cyclic stretch produced IL‐8 in a time‐ and strain‐dependent manner, but there was no observed effect related to stretch frequency. Activation of Rel A and IκBα was detected 10 min after the initiation of stretch, peaked at 15 min and returned to baseline within 1 h. IL‐8 production was partially inhibited by the presence of PDTC. Conclusion: Cyclic mechanical stretch can activate Rel A translocation and IκBα degradation, thus inducing the secretion of IL‐8 in alveolar epithelial type II cells. Pharmacological inhibition of Rel A and IκBα inhibits IL‐8 mRNA and protein levels, suggesting novel approaches to prevent VILI.