Regulation of neutrophil interleukin 8 gene expression and protein secretion by LPS, TNF‐α, and IL‐1β

Seitaro Fujishima, Andrew R. Hoffman, Thanh Vu, K. Jin Kim, Hui Zheng, David Daniel, Youngmee Kim, Ellen F. Wallace, James W. Larrick, Thomas A. Raffin

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Abstract

Neutrophils are possibly involved in the pathogenesis of various lung diseases through the release of numerous mediators. In the present study, we studied the regulation of IL‐8 gene induction and protein secretion in human blood neutrophils. Northern blot analysis revealed that LPS increased IL‐8 mRNA levels in neutrophils, with a maximal fivefold increase by 2 h. IL‐8 mRNA levels returned to baseline value within 12 h. In contrast, LPS‐stimulated monocytes demonstrated a sustained increase of IL‐8 mRNA levels for more than 24 h. TNF‐α, IL‐1β, and phorbol myristate acetate also increased IL‐8 mRNA levels in neutrophils. Immunohistochemical analysis confirmed that IL‐8 was localized within stimulated neutrophils. IL‐8 secretion by neutrophils and monocytes was quantified using a specific ELISA for IL‐8. Resting neutrophils secreted minimal IL‐8 activity. However when cells were stimualted with LPS, TNF‐α, or IL‐1bT, neutrophils secreted IL‐8. IL‐8 secretion was most marked during the first 2 h after stimulation and decreased thereafter. In contrast, monocytes maintained a high rate of IL‐8 secretion over 12 h. Although a single monocyte secreted 70‐fold more IL‐8 than did a single neutrophil after 4 h of incubation, the high abundance of neutrophils in peripheral blood made the neutrophil‐secreted IL‐8 more significant. During the first 2 h, neutrophils secreted ∼40% of the IL‐8 released by monocytes in the same volume of blood. This ratio decreased to 9% after 12 h. Neutrophil‐secreted IL‐8 may play an autocrine or paracrine role during the initial stage of inflammation. © 1993 Wiley‐Liss, Inc.

Original languageEnglish
Pages (from-to)478-485
Number of pages8
JournalJournal of Cellular Physiology
Volume154
Issue number3
DOIs
Publication statusPublished - 1993 Mar

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ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Fujishima, S., Hoffman, A. R., Vu, T., Kim, K. J., Zheng, H., Daniel, D., Kim, Y., Wallace, E. F., Larrick, J. W., & Raffin, T. A. (1993). Regulation of neutrophil interleukin 8 gene expression and protein secretion by LPS, TNF‐α, and IL‐1β. Journal of Cellular Physiology, 154(3), 478-485. https://doi.org/10.1002/jcp.1041540305