Expression and regulation of the CC-chemokine monocyte chemoattractant protein-1 in rat testicular cells in primary culture

Testicular inflammation is classically observed in pathogenesis caused by infectious agents, environmental toxins, trauma, or autoimmune reactions and can lead to transitory or even permanent sterility. In these situations, a leukocyte infiltration is generally encountered. Macrophage inflammatory proteins (MIP)-1 alpha and -1 beta and monocyte chemoattractant protein-1 (MCP-1) are CC-chemokines involved in macrophage and lymphocyte chemoattraction. In the present study, using reverse transcription-polymerase chain reaction, Northern blot, and a specific ELISA, we investigated whether or not these chemokines are present within the testis and whether they are induced by a number of proinflammatory cytokines and lipopolysaccharides (LPS). MIP-1 alpha and MIP-1 beta were not detected in Sertoli cells, germ cells, peritubular cells, or Leydig cells. In contrast, MCP-1 mRNA and protein were found to be expressed by control isolated peritubular cells, and expression was markedly stimulated by interleukin-1 alpha and -1 beta (IL-1 alpha and IL-1 beta), tumor necrosis factor alpha (TNF-alpha), interferon gamma, and LPS. Leydig cells expressed MCP-1 when stimulated by IL-1 beta. In contrast, MCP-1 was not found to be produced by Sertoli cells or germ cells as established by Northern blot and ELISA techniques. The kinetics of MCP-1 production by peritubular cells, as demonstrated by expression as early as 8 h poststimulation, are compatible with there being a rapid mobilization of these cells and this chemokine in an inflammatory process. Moreover, MCP-1 production by peritubular cells after half-maximal stimulation by LPS, TNF-alpha, and IL-1 beta (2 pg/ml-0.9 ng/ml) is also compatible with the physiologic concentrations of the proinflammatory cytokines generally found in an inflammatory site. It is concluded that MCP-1 is produced by Leydig cells and peritubular cells and that it could be involved in the mobilization and migration of leukocytes observed during testicular inflammation.