Necrosis of lung epithelial cells by filarial parasitic protein via an early induction of c-H-ras and TNF alpha expression.
The direct interaction of filarial proteins with lung epithelial cells was examined to determine the possible mechanism of inducing cell death, an event that is observed in patients with tropical pulmonary eosinophilia. Exposure of lung epithelial cells to filarial parasitic proteins, Brugia malayi (BmA), Setaria digitata (Sd), and recombinant filarial protein (pGT 7) in vitro for more than 2 days, causes the appearance of DNA fragments both in the cytoplasm and culture supernatants, while no fragmentation was observed in the untreated controls. The release of DNA fragments both in the cytoplasm and the culture supernatants simultaneously, indicates that cell death is induced by a necrotic event rather than apoptosis. Fluorescent-labelled studies also indicate the fragmentation of DNA increasing in a time-dependent manner. Normal cellular function is controlled through several oncogenes. The modulation of specific proto-oncogenes like myc, ras and TNF alpha during exposure to filarial parasitic proteins reveal elevated levels of expression of ras and TNF alpha as early as 2 hours, implicating their involvement prior to DNA fragmentation leading to pathogenesis.
Maya
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A
Centre for Biotechnology, Anna University, Madras, India.
Jayaraman
K
K
Balakrishnan
A
A
D000818:Animals; D017178:Brugia malayi / Q000737:chemistry*; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000469:parasitology / Q000473:pathology; D005368:Filariasis / Q000469:parasitology* / Q000473:pathology; D007700:Kinetics; D008174:Lung Diseases, Parasitic / Q000469:parasitology* / Q000473:pathology; D008856:Microscopy, Fluorescence; D009336:Necrosis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017182:Setaria Nematode / Q000737:chemistry*; D012719:Setariasis / Q000469:parasitology* / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018631:ras Proteins