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

• Published in: Molecular immunology 2000-02, Vol.37 (3), p.115-123
• Main Authors: Narayanan, Kishore, Balakrishnan, Arun, Miyamoto, Shigeki
• Format: Article
• Language: English
• Subjects: Cytokine; Filarial parasite; I-kappa B; I^KB^a protein; NF-^KB protein; NF-kappa B; sheath proteins; Tropical pulmonary eosinophilia
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/S0161-5890(00)00039-0

The transcription factor NF-κB plays critical roles in immune and inflammatory responses. Here we show that filarial parasitic sheath proteins cause activation of NF-κB in the airway epithelial HEp-2 cell line. This activation was transient and saturable, and involved degradation of the cytoplasmic inhibitor protein IκBα. Stable expression of IκBα mutated at Ser32 and Ser36 to Ala caused inhibition of NF-κB activation, indicating that this activation involves the IκB kinase-mediated pathway. Moreover, while it did not influence the HEp-2 cell survival, selective blockade of NF-κB activation resulted in inhibition of the expression and the secretion of pro-inflammatory cytokines, tumor necrosis factor-α, interleukin-6 and interleukin-8. Thus, initial transient activation of NF-κB resulted in profound and long-term effects on epithelial cell responses to filarial parasitic proteins. These findings implicate an important role for NF-κB in orchestrating inflammatory reactions associated with tropical pulmonary eosinophilia.