The p38 MAPK pathway mediates interleukin-1-induced Sertoli cell proliferation.
We have reported earlier that interleukin-1 (IL-1) is a potent growth factor for immature Sertoli cells (somatic cells in the testis required for testicular development and later spermatogenesis) and that this effect is synergistic with the mitogenic effect of follicle-stimulating hormone (FSH). The aim of the present study was to determine whether MAPK pathways are involved in mediating the mitogenic effect of IL-1 on Sertoli cells. Western blotting revealed that IL-1alpha activated p38 MAPK and JNK/SAPK, but not ERK, in Sertoli cells from 8- or 9-day-old rat. The inhibitor of p38 MAPK SB203580 attenuated the IL-1alpha-induced proliferation of Sertoli cells, as assessed by (3)H-thymidine incorporation and supravital staining as well as by direct cell counting. We conclude that the p38 MAPK pathway mediates the proliferative effect of IL-1alpha on immature Sertoli cells in vitro. Since the mitogenic effect of FSH is mediated via ERK, the synergistic action of IL-1alpha and FSH may be explained by their different intracellular signalling pathways. Induction of IL-1 by inflammation, infection or other tissue injuries may result in testicular damage by interfering with normal Sertoli cell development and thus future spermatogenesis.
Petersen
Cecilia
C
Department of Woman and Child Health, Paediatric Endocrinology Unit, Astrid Lindgren Children's Hospital, Karolinska Institutet, Stockholm, Sweden. cecilia.petersen@lbh.ki.se
Svechnikov
Konstantin
K
Fröysa
Berit
B
Söder
Olle
O
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D012708:Sertoli Cells / Q000187:drug effects / Q000201:enzymology*; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D007375:Interleukin-1; D011725:Pyridines; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C093642:SB 203580