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.