Residual bodies activate Sertoli cell interleukin-1 alpha (IL-1 alpha) release, which triggers IL-6 production by an autocrine mechanism, through the lipoxygenase pathway.
Interleukin-1 (IL-1) and IL-6 are produced by Sertoli cells. As IL-1 stimulates IL-6 production in some tissues, the cascade of events that results in IL-6 secretion by Sertoli cells was studied. The addition of IL-1 alpha to Sertoli cells resulted in a time-dependent increase in IL-6 secretion. Incubation of Sertoli cells with two known stimulators of IL-1 production, lipopolysaccharide (LPS) and residual bodies, resulted in a significant increase in IL-1 release into the medium several hours before IL-6 release. That IL-1 is essential for IL-6 production from Sertoli cells was established by blocking the actions of LPS and residual bodies with an anti-IL-1 alpha antibody. An increase in the release of IL-1 before IL-6 was also observed in medium obtained from staged segments of intact seminiferous tubules; IL-1 reached a maximum level at stage VIII, when mature spermatozoa are released and residual bodies are formed and phagocytosed. The secretion of IL-6 was low during this stage and then increased progressively from stage IX onward, consistent with IL-1 stimulation of IL-6. The pathway of IL-1 alpha-induced release of IL-6 was studied in the presence of agents that influence arachidonic acid release and metabolism. IL-1 alpha was found to stimulate arachidonic acid release by Sertoli cells. Furthermore, a phospholipase A2 inhibitor, aristolochic acid, significantly decreased IL-1-, LPS-, and pyrularia pubera thionin-induced IL-6 secretion from Sertoli cells. Indomethacin, a specific inhibitor of the cyclooxygenase pathway, had no significant effect on basal, but enhanced IL-1- and LPS-stimulated IL-6 production. The involvement of arachidonic acid metabolites produced in the lipoxygenase pathway on the release of IL-6 was investigated indirectly, using nordihydroguaiaretic acid. This inhibitor reduced basal and IL-1 alpha- and LPS-stimulated IL-6 production. Ethacrynic acid, an inhibitor of peptido-leukotriene synthesis, also reduced basal IL-6 levels and blocked IL-1 alpha- as well as LPS-induced IL-6 secretion. It is concluded that IL-1 produced by Sertoli cells in response to LPS or residual bodies induces IL-6 through the lipoxygenase pathway.
Syed
V
V
Groupe d'Etude de la Reproduction chez le Mâle (GERM)-INSERM U-435, Université de Rennes 1, France.
Stéphan
J P
JP
Gérard
N
N
Legrand
A
A
Parvinen
M
M
Bardin
C W
CW
Jégou
B
B
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003593:Cytoplasm / Q000502:physiology; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000378:metabolism*; D013087:Spermatids / Q000648:ultrastructure
D000906:Antibodies; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D008084:Lipoxygenase