Interleukin-8 stimulates the formation of 15-hydroxy-eicosatetraenoic acid by human neutrophils in vitro.
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 degrees 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.
Fogh
K
K
Department of Dermatology, Marselisborg Hospital, University of Aarhus, Denmark.
Larsen
C G
CG
Iversen
L
L
Kragballe
K
K
D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000494:pharmacology*; D008055:Lipids / Q000302:isolation & purification; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism
D006893:Hydroxyeicosatetraenoic Acids; D016209:Interleukin-8; D008055:Lipids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid