NF-kappa B is essential for induction of pro-inflammatory cytokine genes by filarial parasitic sheath proteins

The transcription factor NF-kappa B plays critical roles in immune and infl ammatory responses. Here we show that filarial parasitic sheath proteins ca use activation of NF-kappa B in the airway epithelial HEp-2 cell line. This activation was transient and saturable, and involved degradation of the cy toplasmic inhibitor protein I kappa B alpha. Stable expression of I kappa B alpha mutated at Ser32 and Ser36 to Ala caused inhibition of NF-kappa B ac tivation, indicating that this activation involves the I kappa B kinase-med iated pathway. Moreover, while it did not influence the HEp-2 cell survival , selective blockade of NF-kappa B activation resulted in inhibition of the expression and the secretion of pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-6 and interleukin-8. Thus, initial transient act ivation of NF-kappa B resulted in profound and long-term effects on epithel ial cell responses to filarial parasitic proteins. These findings implicate an important role for NF-kappa B in orchestrating inflammatory reactions a ssociated with tropical pulmonary eosinophilia. (C) 2000 Elsevier Science L td. All rights reserved.