Induction of IL-6 in co-culture of bronchial epithelial cells and eosinophils is regulated by p38 MAPK and NF-kappaB.
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-kappaB (NF-kappaB) 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)kappaB-alpha 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-IkappaB-alpha and activity of NF-kappaB in BEAS-2B cells. NF-kappaB 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-kappaB, 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.
Wang
C B
CB
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Wong
C K
CK
Ip
W K
WK
Li
M L Y
ML
Tian
Y P
YP
Lam
C W K
CW
D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D004804:Eosinophils / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D005557:Formaldehyde; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D011108:Polymers; D015854:Up-Regulation / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D015850:Interleukin-6; D016328:NF-kappa B; D011108:Polymers; D005557:Formaldehyde; D048051:p38 Mitogen-Activated Protein Kinases; C003043:paraform