Interleukin-1-mediated release of interleukin-8 by asbestos-stimulated human pleural mesothelial cells.
The pleuropulmonary response to inhaled asbestos frequently involves inflammation and release of various cytokines from lung cells. Among these, interleukin-8 (IL-8) released from the mesothelium could augment inflammation of the pleura by attracting neutrophils to the pleural space. We used cultures of human pleural mesothelial cells (HPMC) to examine the mechanism of IL-8 production by asbestos and cytokines. Suspensions of amosite, chrysotile, or crocidolite asbestos in concentrations as low as 5 micrograms/ml enhanced release of IL-8 from HPMC during 6 h of incubation at 37 degrees C. Electron microscopy of asbestos-treated HPMC showed that the cells avidly engulfed each of the different types of asbestos fibers. Two proinflammatory cytokines, interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha, enhanced IL-8 release within 2 h and had an even greater effect after 6 h. Release of IL-8 was measured by an enzyme-linked immunosorbent assay, and functional activity of the cytokine was assessed by chemotaxis of human neutrophils. Identity of IL-8 in HPMC supernatants was established by absorption with an antibody to IL-8. Preincubation of HPMC with IL-1 receptor antagonist (IL-1ra) significantly decreased release of IL-8 after stimulation with amosite or crocidolite asbestos. We conclude that HPMC release IL-8 in response to asbestos stimulation and that the response is, in part, mediated by IL-1, mainly in the form of IL-1 alpha.
Griffith
D E
DE
Department of Medicine, University of Texas Health Center, Tyler 75710.
Miller
E J
EJ
Gray
L D
LD
Idell
S
S
Johnson
A R
AR
D000911:Antibodies, Monoclonal; D001194:Asbestos / Q000633:toxicity*; D017639:Asbestos, Amosite / Q000633:toxicity; D017638:Asbestos, Crocidolite / Q000633:toxicity; D017632:Asbestos, Serpentine / Q000633:toxicity; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism*; D017348:Microscopy, Electron, Scanning Transmission; D010587:Phagocytosis; D010994:Pleura / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D017632:Asbestos, Serpentine; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D017638:Asbestos, Crocidolite; D017639:Asbestos, Amosite; D001194:Asbestos