Induction of IL-6 in co-culture of bronchial epithelial cells and eosinophils is regulated by p38 MAPK and NF-κB
Authors: Wang, C. B.; Wong, C. K.1; Ip, W. K.1; Li, M. L. Y.1; Tian, Y. P.2; Lam, C. W. K.1
Source: Allergy, Volume 60, Number 11, November 2005 , pp. 1378-1385(8)
Publisher: Blackwell Publishing
Abstract:
Background: Prominent infiltration of eosinophils into the airway mucosa and release of inflammatory mediators upon their adhesion onto airway epithelial cells are the immunopathogical mechanisms of allergic asthma. Objective: We investigated the effect of normal and paraformaldyhyde-fixed human eosinophils on BEAS-2B cells, a human bronchial epithelial cell line, for the release of inflammatory cytokine interleukin (IL)-6. Methods: Interleukin-6 in cell culture supernatant, protein amount of p38 mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) activity in BEAS-2B cells were analyzed by Western blot and enzyme-linked immunosorbent assay (ELISA). IL-6 gene expression was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), and p38 MAPK activity and inhibitor (I)κB-α induction were evaluated by Western blot. Results: Co-culture of BEAS-2B cells and eosinophils induced a significant elevation of IL-6 expression in BEAS-2B cells. Interaction of eosinophils and BEAS-2B cells led to a marked induction in phospho-p38 MAPK, phospho-IκB-α and activity of NF-κB in BEAS-2B cells. NF-κB inhibitor BAY 11-7082 and p38 MAPK inhibitor SB 203580 significantly decreased IL-6 release in a co-culture of BEAS-2B cells and eosinophils. Fixed human eosinophils were able to maintain their ability to induce IL-6 release in co-culture, activate p38 MAPK and NK-κB, and up-regulate IL-6 gene expression in BEAS-2B cells. Conclusions: These data indicate that the interaction of eosinophils and bronchial epithelial cells plays an important role in airway inflammation, at least partly, via IL-6 induction.Keywords: eosinophils; epithelial cells; IL-6; NF-κB; p38 MAPK
Document Type: Research article
DOI: 10.1111/j.1398-9995.2005.00884.x
Affiliations: 1: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong 2: Department of Clinical Biochemistry, Chinese People's Liberation Army General Hospital & Postgraduate Medical School, Beijing, China

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