Superoxide Mediates Cigarette Smoke-Induced Infiltration of Neutrophils into the Airways through Nuclear Factor-κ B Activation and IL-8 mRNA Expression in Guinea Pigs In Vivo
Abstract
We examined the hypothesis that superoxide mediates infiltration of neutrophils to the airways through nuclear factor (NF)-κB and interleukin-8 (IL-8) after acute exposure to cigarette smoke (CS) in vivo. Male Hartley strain guinea pigs were exposed to air or 20 puffs of CS and killed 5 h after the exposure. The differential cell count of bronchoalveolar lavage fluid and specific myeloperoxidase enzyme assay demonstrated that acute exposure to CS caused neutrophil accumulation to the airways and parenchyma, respectively. Acute exposure to CS increased DNA-binding activity of NF-κB in the lung. Acute exposure to CS also increased IL-8 messenger RNA (mRNA) expression in the lung. Pretreatment of guinea pigs with recombinant human superoxide dismutase (rhSOD) aerosols reduced the CS-induced neutrophil accumulation to the airways. Both activation of NF-κB and increased IL-8 mRNA expression were also inhibited by the pretreatment of rhSOD aerosols. Strong immunoreactivities for p65 and p50 were detected in the nuclei of alveolar macrophages after acute exposure to CS. The signal for IL-8 mRNA expression was demonstrated in the alveolar space after acute exposure to CS. Neither significant immunoreactivities for p65 and p50 nor IL-8 mRNA signals were observed in airway epithelium. These observations suggest that acute exposure to CS initiates superoxide-dependent mechanism that, through NF-κB activation and IL-8 mRNA expression, produces infiltration of neutrophils to the airways in vivo. It was also suggested that the alveolar macrophage is one potential source of NF-κB activation and IL-8 mRNA expression after acute exposure to CS.
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Pretreatment of guinea pigs with Mn-based mimetic complex reduces both smoking-induced expression of IL-8 and activation of NF-κB.
“Pretreatment of guinea pigs with Mn-based mimetic complex reduces both smoking-induced expression of IL-8 and activation of NF-κB (Nishikawa et al. 1999).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Nishikawa et al. 1999
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- Authors
- Nishikawa, M., Kakemizu, N., Ito, T., Kudo, M., Kaneko, T., Suzuki, M., Udaka, N., Ikeda, H., & Okubo, T.
- Affiliations
- Yokohama City University (JP)
- Corresponding author
- Nishikawa, Masanori
- Venue
- American Journal of Respiratory Cell and Molecular Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-02-01
- Volume
- 20
- Issue
- 2
- Pages
- 189-198
- ISSN
- 1044-1549 (ISSN-L)
- 1535-4989
- OpenAlex
- W2066349836
- Cited by
- 124
- References
- 39
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2012: 6
- FWCI
- 10.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- cigarette smoke, superoxide, neutrophil infiltration, respiratory tract, NF-κB activation, interleukin-8, superoxide dismutase, alveolar macrophages, acute lung injury, bronchoalveolar lavage, oxidative stress
- MeSH terms
- Animals, Base Sequence, Cell Movement, Guinea Pigs, Immunohistochemistry, Male, Molecular Sequence Data, Neutrophils, Recombinant Proteins, RNA, Messenger, Smoke, Superoxides, Superoxide Dismutase, Trachea, Interleukin-8, NF-kappa B, Reverse Transcriptase Polymerase Chain Reaction
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