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Interleukin-8 stimulates the formation of 15-hydroxy-eicosatetraenoic acid by human neutrophilsin vitro

  • Inflammation and Immunomodulation
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Abstract

Interleukin-8 (IL-8), is a potent activator of polymorphonuclear leukocyte (PMN) functions including chemotaxis, superoxide anion production, and enzyme release and it is also chemotactic for lymphocytes. Additionally, it has recently been shown that IL-8 stimulates the formation of 5-lipoxygenase (LO) products of arachidonic acid (AA) by human PMNs. The purpose of the present study was to determine whether IL-8 also might affect the formation of 15-LO products from AA. Purified PMNs in phosphate buffered saline were preincubated with and without exogenous AA (10−5–10−4 M) for 10 min. Then IL-8 was added in biologically relevant concentrations ranging from 0.1 to 100 ng/ml and incubation was carried out for 5 min at 37°C. Lipids were then extracted from supernatants, and eicosanoids were determined by quantitative RP-HPLC. Compared with unstimulated cells, IL-8 resulted in a dose dependent increase in both LTB4 and 15-HETE (up to 125% and 40% at 100 ng/ml, respectively). This increase in eicosanoid formation required the presence of exogenous AA. These results indicate that IL-8 is both a potent stimulator of 5-LO activity and of 15-LO activity. LTB4 can induce both inflammation and contribute to hyperproliferation in the skin. 15-HETE in contrast has the ability to inhibit the effects induced by LTB4. Because IL-8 is able to stimulate both LTB4 and 15-HETE formation, the effect of IL-8 as a putative regulator of inflammatory processes may be dependent on the relative stimulation of 5-LO and 15-LO.

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Author notes

  1. K. Fogh

    Present address: Department of Dermatology, Kresge I, University of Michigan Medical Center, Box 0528, 48109-0528, Ann Arbor, Michigan, USA

Authors and Affiliations

  1. Department of Dermatology, Marselisborg Hospital, University of Aarhus, Aarhus, Denmark

    K. Fogh, C. G. Larsen, L. Iversen & K. Kragballe

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  2. C. G. Larsen
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  3. L. Iversen
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  4. K. Kragballe
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Fogh, K., Larsen, C.G., Iversen, L. et al. Interleukin-8 stimulates the formation of 15-hydroxy-eicosatetraenoic acid by human neutrophilsin vitro . Agents and Actions 35, 227–231 (1992). https://doi.org/10.1007/BF01997504

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  • DOI: https://doi.org/10.1007/BF01997504

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