Expression and regulation of the CXC-chemokines, GRO/KC and IP-10/mob-1 in rat seminiferous tubules.

ABSTRACT

Testicular inflammation is classically observed in the pathogenesis of viral and bacterial infection or tumoral invasion. In these situations, leukocyte infiltration is generally encountered. GRO/KC (growth-related oncogene) and IP-10/mob-1 (IFN-gamma-inducible protein) are two CXC-chemokines which attract neutrophils and activated T lymphocytes, respectively, have been studied for their ability to participate to testicular inflammation (orchitis). In the present work, using Northern blot and immunocytochemistry, we aimed to investigate whether GRO/KC and IP-10/mob-1 are produced within the seminiferous tubules of the testis and if these chemokines are induced by a number of pro-inflammatory cytokines and lipopolysaccharides (LPS). Our results show that GRO/KC and IP-10/mob-1 mRNAs were never found in germ cells, whether they were stimulated or not. In contrast, GRO/KC mRNA was expressed by isolated peritubular cells when stimulated by interleukin-1 alpha and beta (IL-1 alpha and IL-1 beta) or LPS and to a lesser extent by tumor necrosis factor-alpha (TNF-alpha) and by Sertoli cells when the latter were stimulated by rIL-alpha and rIL-1 beta and to a lesser extent by TNF-alpha and LPS. Moreover, IP10/mob-1 transcripts were strongly induced in peritubular cells by interferon-alpha (IFN-alpha) and IFN-gamma, whereas, in isolated Sertoli cells, INF-alpha and TNF-alpha were the only potent inducers. The kinetics of GRO/KC and IP-10/mob-1 mRNA expression by peritubular and Sertoli cells (significant stimulation as early as 1 hour and 4 hours post-exposure to the stimuli, respectively) are compatible with the hypothesis of a rapid mobilisation of these cells in an inflammatory process. Moreover, the dose-dependent effects of pro-inflammatory cytokines to induce a chemokine response were compatible with a high sensitivity of peritubular and Sertoli cells in orchitis. In conclusion, this present study shows that 2 CXC-chemokines, GRO/KC and IP10/mob-1, are produced by testicular somatic cells of seminiferous tubules, strongly indicating a likely role of these chemokines in the accumulation of neutrophils and T lymphocytes during orchitis of various origins.