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Induction of Interleukin 8 (IL‐8) Production by Pseudomonas Nitrite Reductase in Human Alveolar Macrophages and Epithelial Cells
Author(s) -
Sar Borann,
Oishi Kazunori,
Matsushima Kouji,
Nagatake Tsuyoshi
Publication year - 1999
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.1999.tb02424.x
Subject(s) - biology , nitrite , microbiology and biotechnology , nitrate reductase , interleukin , nitrite reductase , pseudomonas , immunology , interleukin 8 , cytokine , biochemistry , enzyme , bacteria , nitrate , ecology , genetics
Interleukin‐8 (IL‐8) participates in the generation of dense neutrophil accumulations in bronchopulmonary infections caused by Pseudomonas aeruginosa ( P. aeruginosa ). We have recently reported that nitrite reductase, a bifunctional enzyme located in the periplasmic space of P. aeruginosa , induces IL‐8 generation in bronchial epithelial cells (K. Oishi et al. Infect. Immun. 65: 2648 2655, 1997). We examined whether or not Pseudomonas nitrite reductase (PNR) could also stimulate human alveolar macrophages (AM) and pulmonary type II epithelial‐like cells (A549) to induce IL‐8 production and mRNA expression as well as the production of TNFα and IL‐1β. We demonstrated a time‐ and dose‐dependent IL‐8 protein synthesis and IL‐8 mRNA expression, but no TNFα or IL‐1β production, by A549 cells in response to PNR. New protein translation was not required for PNR‐mediated IL‐8 mRNA expression in the same cells. Furthermore, simultaneous stimulation of PNR with serial doses of TNFα or IL‐1β resulted in additive IL‐8 production in A549 cells. In adherent AM, PNR enhanced IL‐8 protein synthesis and IL‐8 mRNA expression in a time‐dependent fashion. PNR similarly induced a time‐dependent production of TNFα and IL‐1β by human adherent AM. Neutralization of TNFα or IL‐1β did not influence the levels of IL‐8 production in adherent AM culture. We also evaluated whether the culture supernatants of the A549 cells or AM stimulated with PNR could similarly mediate neutrophil migration in vitro . When anti‐human IL‐8 immunoglobulin G was used for neutralizing neutrophil chemotactic factor (NCF) activities in the culture supernatants of these cells stimulated with 5 μg/ml of PNR, the mean percent reduction of NCF activities were 49‐59% in A549 cells and 2434% in AM. Our present data support that PNR directly stimulates AM and pulmonary epithelial cells to produce IL‐8. PNR also mediates neutrophil migration, in part, through IL‐8 production from AM and pulmonary epithelial cells. These data suggest the contribution of PNR to the pathogenesis of bronchopulmonary infections due to P. aeruginosa .