Interleukin 1β expression is stimulated by Toll-like receptor pathway activation and spermatogenic cells in mouse Sertoli cells cultured in vitro. (#220)
Spermatogenesis relies on communication between developing germ cells and supporting Sertoli cells, and cytokines play an important role during spermatogenesis under normal physiological conditions. In the rat, inflammatory cytokines, including interleukin (IL)1α, IL6 and activin A, are regulated throughout the cycle of the seminiferous epithelium, but IL1β is not normally expressed. Both IL1 forms regulate testicular steroidogenesis and testosterone output, tight junction formation, and production of IL6 and activin A by the Sertoli cell. However, during inflammation, Toll-like receptor (TLR) pathways are activated and inflammatory cytokine synthesis can be broadly up-regulated in the testis, thereby interfering with normal spermatogenesis and steroidogenesis.
A TLR signalling pathway PCR array was carried out on primary mouse Sertoli cell cultures treated with the TLR4 ligand, lipopolysaccharide (LPS) for 3h. The expression of TLR pathway components (TLR1,2,3, MyD88, NFκB) and several cytokines (IL1α, IL1β, IL6, IL10, IL12α, IFNβ1, TNFα) were induced. Notably, IL1β expression was highly up-regulated (~300 fold) following LPS treatment (0-100μg/ml) by 3h, and peaked at 6h before decreasing over a 24h time-course. Pam3Cys and PolyI:C, which signal through TLR2 and TLR3 respectively, did not induce IL1β expression.
Analyses of IL1α and IL1β expression from primary mouse Sertoli cells co-cultured with purified intact germ cells over a time-course (3, 6, 9hr) showed that expression of IL1α or IL1β was dependant on the developmental stage, where pachytene spermatocytes stimulated IL1α preferentially and round spermatids stimulated the highest levels of IL1β expression.
In summary, in contrast to the rat, mouse Sertoli cells produce high levels of IL1β following activation of TLR4. Moreover there appears to be a post-meiotic switch in the form of IL1 produced by Sertoli-germ cell co-cultures, from cell-associated IL1α to the secreted form, IL1β. This may indicate a shift in the principal cellular target of IL1 during meiosis in the mouse testis.