TNF-alpha increases tracheal epithelial asbestos and fiberglass binding via a NF-kappaB-dependent mechanism.
Tumor necrosis factor (TNF)-alpha is released from alveolar macrophages after phagocytosis of mineral fibers. To determine whether TNF-alpha affects the binding of fibers to epithelial cells, we exposed rat tracheal explants to TNF-alpha or to culture medium alone, followed by a suspension of amosite asbestos or fiberglass (MMVF10). Loosely adherent fibers were removed from the surface with a standardized washing technique, and the number of bound fibers was determined by scanning electron microscopy. Increasing doses of TNF-alpha produced increases in fiber binding. This effect was abolished by an anti-TNF-alpha antibody, the proteasome inhibitor MG-132, and the nuclear factor (NF)-kappaB inhibitor pyrrolidine dithiocarbamate. Gel shift and Western blot analyses confirmed that TNF-alpha activated NF-kappaB and depleted IkappaB in this system and that these effects were prevented by MG-132 and pyrrolidine dithiocarbamate. These observations indicate that TNF-alpha increases epithelial fiber binding by a NF-kappaB-dependent mechanism. They also suggest that mineral particles may cause pathological lesions via an autocrine-like process in which the response evoked by particles, for example, macrophage TNF-alpha production, acts to enhance subsequent interactions of particles with tissue.
Xie
C
C
Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada V6T 2B5.
Reusse
A
A
Dai
J
J
Zay
K
K
Harnett
J
J
Churg
A
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017639:Asbestos, Amosite / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005898:Glass; D007976:Leupeptins / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D007976:Leupeptins; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C009753:fiberglass; D017639:Asbestos, Amosite; C020972:pyrrolidine dithiocarbamic acid; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde