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

Testicular inflammation is classically observed in the pathogenesis of vira l and bacterial infection or tumoral invasion. In these situations, leukocy te 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 s tudied for their ability to participate to testicular inflammation (orchiti s). In the present work, using Northern blot and immunocytochemistry, we ai med to investigate whether GRO/KC and IP-10/mob-1 are produced within the s eminiferous tubules of the testis and if these chemokines are induced by a number of pro-inflammatory cytokines and lipopolysaccharides (LPS), Our res ults 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 expresse d 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 nec rosis factor-alpha (TNP-alpha) and by Sertoli cells when the latter were st imulated by rIL-alpha and rIL-1 beta and to a lesser extent by TNF-or and L PS, Moreover, IP10/mob-1 transcripts were strongly induced in peritubular c ells by interferon-alpha (IFN-alpha) and IFN-gamma, whereas, in isolated Se rtoli cells, INF-alpha and TNF-alpha were the only potent inducers. The kin etics of GRO/KC and IP10/mob-1 mRNA expression by peritubular and Sertoli c ells (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 resp onse were compatible with a high sensitivity of peritubular and Sertoli cel ls in orchitis, In conclusion, this present study shows that 2 CXC-chemokin es, GRO/KC and IP10/mob-1, are produced by testicular somatic cells of semi niferous tubules, strongly indicating a likely role of these chemokines in the accumulation of neutrophils and T lymphocytes during orchitis of variou s origins.