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

✍ Scribed by 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

Publisher
John Wiley and Sons
Year
1993
Tongue
English
Weight
805 KB
Volume
154
Category
Article
ISSN
0021-9541

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✦ Synopsis

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 b y 2 h . IL-8 mRNa levels returned to baseline values within 1 2 h. In contrast, LPS-stimulated monocytes demonstrated a sustained increase of IL-8 mRNA levels for more than 24 ti. TNF-a, IL-1 p, and phorbol niyristate acetate also increased IL-8 mRNA levels in neutrophils. Immunohistochemical analysis confirmed that IL-8 was localized wthin stimulated neutrophils. IL-8 secretion by neutrophils and monocytes was quantified using a specific ELlSA for IL-8. Resting neutrophils secreted minimal IL-8 activity. However when cells were stimualted with LPS, TNF-a, or IL-lB, ncutrophils 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.

Q 19Y3 Wiley-Liss, Inc.

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