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Infection and Immunity, August 1999, p. 3872-3878, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Essential Role of Transcription Factor Nuclear Factor-kappa B in Regulation of Interleukin-8 Gene Expression by Nitrite Reductase from Pseudomonas aeruginosa in Respiratory Epithelial Cells

Naoki Mori,1,* Kazunori Oishi,2 Borann Sar,2 Naofumi Mukaida,3 Tsuyoshi Nagatake,2 Kouji Matsushima,4 and Naoki Yamamoto1

Department of Preventive Medicine and AIDS Research1 and Department of Internal Medicine,2 Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Department of Pharmacology, Cancer Research Institute, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-0934,3 and Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033,4 Japan

Received 4 January 1999/Returned for modification 12 March 1999/Accepted 27 May 1999

Persistent infection with Pseudomonas aeruginosa increases interleukin-8 (IL-8) levels and causes dense neutrophil infiltrations in the airways of patients with chronic airway diseases. Recently, we have reported that nitrite reductase from P. aeruginosa induces the production of IL-8 in respiratory cells, including bronchial epithelial cells. To determine the molecular mechanism(s) of nitrite reductase-induced IL-8 expression in respiratory cells, A549 epithelial cells were transfected with plasmids containing serial deletions of the 5'-flanking region of the IL-8 gene and then exposed to nitrite reductase. Nitrite reductase significantly enhanced IL-8 gene promoter-driven reporter activity. This increased IL-8 gene expression was inhibited by mutating the nuclear factor-kappa B (NF-kappa B) binding element. Nitrite reductase enhanced nuclear localization of the NF-kappa B binding complex. Furthermore, nitrite reductase induced the degradation of Ikappa Balpha , the major cytoplasmic inhibitor of NF-kappa B, and the expression of Ikappa Balpha mRNA. These data support the critical role of the activation of NF-kappa B in nitrite reductase-induced IL-8 gene expression in airway epithelium.

* Corresponding author. Mailing address: Department of Preventive Medicine and AIDS Research, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Phone: 81-95-849-7846. Fax: 81-95-849-7805. E-mail: n-mori{at}net.nagasaki-u.ac.jp.

Infection and Immunity, August 1999, p. 3872-3878, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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