Endocrinology, Vol 136, 3070-3078, Copyright © 1995 by Endocrine Society

ARTICLES

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

V Syed, JP Stephan, N Gerard, A Legrand, M Parvinen, CW Bardin and B Jegou
Groupe d'Etude de la Reproduction chez le Male (GERM)-INSERM U-435, Universite de Rennes 1, France.

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.

This article has been cited by other articles:

				L. O'Donnell, K. Pratis, A. Wagenfeld, U. Gottwald, J. Muller, G. Leder, R. I. McLachlan, and P. G. Stanton Transcriptional Profiling of the Hormone-Responsive Stages of Spermatogenesis Reveals Cell-, Stage-, and Hormone-Specific Events Endocrinology, November 1, 2009; 150(11): 5074 - 5084. [Abstract] [Full Text] [PDF]

				O. Sarkar, P. P. Mathur, C. Y. Cheng, and D. D. Mruk Interleukin 1 Alpha (IL1A) Is a Novel Regulator of the Blood-Testis Barrier in the Rat Biol Reprod, March 1, 2008; 78(3): 445 - 454. [Abstract] [Full Text] [PDF]

				T. Ishikawa and P. L. Morris Interleukin-1{beta} Signals through a c-Jun N-Terminal Kinase-Dependent Inducible Nitric Oxide Synthase and Nitric Oxide Production Pathway in Sertoli Epithelial Cells Endocrinology, November 1, 2006; 147(11): 5424 - 5430. [Abstract] [Full Text] [PDF]

				Y Okuma, A E O'Connor, T Hayashi, K L Loveland, D M de Kretser, and M P Hedger Regulated production of activin A and inhibin B throughout the cycle of the seminiferous epithelium in the rat. J. Endocrinol., August 1, 2006; 190(2): 331 - 340. [Abstract] [Full Text] [PDF]

				V. Roulet, H. Denis, C. Staub, A. Le Tortorec, B. Delaleu, A.P. Satie, J.J. Patard, B. Jegou, and N. Dejucq-Rainsford Human testis in organotypic culture: application for basic or clinical research Hum. Reprod., June 1, 2006; 21(6): 1564 - 1575. [Abstract] [Full Text] [PDF]

				T. Ishikawa and P. L. Morris A Multistep Kinase-Based Sertoli Cell Autocrine-Amplifying Loop Regulates Prostaglandins, Their Receptors, and Cytokines Endocrinology, April 1, 2006; 147(4): 1706 - 1716. [Abstract] [Full Text] [PDF]

				C. Fiorini, X. Decrouy, N. Defamie, D. Segretain, and G. Pointis Opposite regulation of connexin33 and connexin43 by LPS and IL-1{alpha} in spermatogenesis Am J Physiol Cell Physiol, March 1, 2006; 290(3): C733 - C740. [Abstract] [Full Text] [PDF]

				T. Ishikawa, K. Hwang, D. Lazzarino, and P. L. Morris Sertoli Cell Expression of Steroidogenic Acute Regulatory Protein-Related Lipid Transfer 1 and 5 Domain-Containing Proteins and Sterol Regulatory Element Binding Protein-1 Are Interleukin-1{beta} Regulated by Activation of c-Jun N-Terminal Kinase and Cyclooxygenase-2 and Cytokine Induction Endocrinology, December 1, 2005; 146(12): 5100 - 5111. [Abstract] [Full Text] [PDF]

				Y Okuma, A E O'Connor, J A Muir, P G Stanton, D M de Kretser, and M P Hedger Regulation of activin A and inhibin B secretion by inflammatory mediators in adult rat Sertoli cell cultures J. Endocrinol., October 1, 2005; 187(1): 125 - 134. [Abstract] [Full Text] [PDF]

				Y Okuma, K Saito, A E O'Connor, D J Phillips, D M de Kretser, and M P Hedger Reciprocal regulation of activin A and inhibin B by interleukin-1 (IL-1) and follicle-stimulating hormone (FSH) in rat Sertoli cells in vitro J. Endocrinol., April 1, 2005; 185(1): 99 - 110. [Abstract] [Full Text] [PDF]

				L. Walch and P. L. Morris Cyclooxygenase 2 Pathway Mediates IL-1{beta} Regulation of IL-1{alpha}, -1{beta}, and IL-6 mRNA Levels in Leydig Cell Progenitors Endocrinology, September 1, 2002; 143(9): 3276 - 3283. [Abstract] [Full Text] [PDF]

				K. Saito, L. O'Donnell, R. I. McLachlan, and D. M. Robertson Spermiation Failure Is a Major Contributor to Early Spermatogenic Suppression Caused by Hormone Withdrawal in Adult Rats Endocrinology, August 1, 2000; 141(8): 2779 - 2785. [Abstract] [Full Text] [PDF]

				D. Zeyse, E. Lunenfeld, M. Beck, I. Prinsloo, and M. Huleihel Induction of Interleukin-1{alpha} Production in Murine Sertoli Cells by Interleukin-1 Biol Reprod, May 1, 2000; 62(5): 1291 - 1296. [Abstract] [Full Text]

				D. Zeyse, E. Lunenfeld, M. Beck, I. Prinsloo, and M. Huleihel Interleukin-1 Receptor Antagonist Is Produced by Sertoli Cells in Vitro Endocrinology, April 1, 2000; 141(4): 1521 - 1527. [Abstract] [Full Text] [PDF]

				L. M. Grønning, J. E. Wang, A. H. Ree, T. B. Haugen, K. Taskén, and K. A. Taskén Regulation of Tissue Inhibitor of Metalloproteinases-1 in Rat Sertoli Cells: Induction by Germ Cell Residual Bodies, Interleukin-1{alpha}, and Second Messengers Biol Reprod, April 1, 2000; 62(4): 1040 - 1046. [Abstract] [Full Text]

				C. Piquet-Pellorce, I. Dorval-Coiffec, M.-D. Pham, and B. Jegou Leukemia Inhibitory Factor Expression and Regulation within the Testis Endocrinology, March 1, 2000; 141(3): 1136 - 1141. [Abstract] [Full Text] [PDF]

				D. Nehar, C. Mauduit, F. Boussouar, and M. Benahmed Interleukin 1{alpha} Stimulates Lactate Dehydrogenase A Expression and Lactate Production in Cultured Porcine Sertoli Cells Biol Reprod, December 1, 1998; 59(6): 1425 - 1432. [Abstract] [Full Text]

				C. M. Telleria, J. Ou, N. Sugino, S. Ferguson, and G. Gibori The Expression of Interleukin-6 in the Pregnant Rat Corpus Luteum and Its Regulation by Progesterone and Glucocorticoid Endocrinology, August 1, 1998; 139(8): 3597 - 3605. [Abstract] [Full Text] [PDF]

				C. Cudicini, H. Kercret, A.-M. Touzalin, F. Ballet, and B. Jegou Vectorial Production of Interleukin 1 and Interleukin 6 by Rat Sertoli Cells Cultured in a Dual Culture Compartment System Endocrinology, July 1, 1997; 138(7): 2863 - 2870. [Abstract] [Full Text] [PDF]

				C. Cudicini, H. Lejeune, E. Gomez, E. Bosmans, F. Ballet, J. Saez, and B. Jegou Human Leydig Cells and Sertoli Cells Are Producers of Interleukins-1 and -6 J. Clin. Endocrinol. Metab., May 1, 1997; 82(5): 1426 - 1433. [Abstract] [Full Text] [PDF]