NF-kappaB is essential for induction of pro-inflammatory cytokine genes by filarial parasitic sheath proteins.
The transcription factor NF-kappaB plays critical roles in immune and inflammatory responses. Here we show that filarial parasitic sheath proteins cause activation of NF-kappaB in the airway epithelial HEp-2 cell line. This activation was transient and saturable, and involved degradation of the cytoplasmic inhibitor protein IkappaBalpha. Stable expression of IkappaBalpha mutated at Ser32 and Ser36 to Ala caused inhibition of NF-kappaB activation, indicating that this activation involves the IkappaB kinase-mediated pathway. Moreover, while it did not influence the HEp-2 cell survival, selective blockade of NF-kappaB 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 activation of NF-kappaB resulted in profound and long-term effects on epithelial cell responses to filarial parasitic proteins. These findings implicate an important role for NF-kappaB in orchestrating inflammatory reactions associated with tropical pulmonary eosinophilia.
Narayanan
K
K
Center for Biotechnology, Anna University, Chennai 600 025, India.
Balakrishnan
A
A
Miyamoto
S
S
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004802:Eosinophilia / Q000276:immunology; D005368:Filariasis / Q000276:immunology; D015801:Helminth Proteins / Q000276:immunology*; D006801:Humans; D020672:I-kappa B Proteins; D008099:Liver / Q000166:cytology / Q000276:immunology; D008174:Lung Diseases, Parasitic / Q000276:immunology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology; D017182:Setaria Nematode / Q000276:immunology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D015801:Helminth Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha