Hedger Mark, Klug Jörg, Fröhlich Suada, Müller Ruth, Meinhardt Andreas
Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia.
J Androl. 2005 May-Jun;26(3):379-86. doi: 10.2164/jandrol.04149.
Leydig cells have been implicated in several inflammation-related responses of the testis. Specifically, these cells produce the proinflammatory cytokines interleukin-1 (IL-1) and IL-6, stimulate macrophage recruitment, and promote interstitial fluid formation. In addition, the immunoregulatory cytokines macrophage migration inhibitory factor (MIF), transforming growth factor-beta1 (TGFbeta1), and interferon-gamma (IFNgamma) are constitutively expressed by testicular cells, including the Leydig cells. In the present study, the contribution of the Leydig cell to testicular inflammatory responses was examined in adult male rats treated with the Leydig cell-specific toxin, ethane dimethane sulfonate (EDS). Intratesticular testosterone levels were modulated by subcutaneous testosterone implants. After 10 days, animals received an injection of lipopolysaccharide (LPS) to induce an inflammatory response, or saline alone, and were killed 3 hours later. Both depletion of Leydig cells by EDS and LPS treatment caused a decrease in collected testicular interstitial fluid to about 35% of control levels, but the effects were not additive. Maintenance of intratesticular testosterone reversed the interstitial fluid decline following EDS treatment and partially prevented the LPS-induced effect. MIF, TGFbeta1, and IFNgamma were expressed in both the normal and inflamed testis at similar levels. In contrast, EDS treatment caused a significant decline in expression of all 3 cytokines, which was prevented by the testosterone implants. These data indicate that 1) expression of TGFbeta1, MIF, and IFNgamma in the testis is not dependent on the presence of intact Leydig cells but is under direct testosterone control and 2) the decline in testicular interstitial fluid during inflammation involves the Leydig cells, acting via both androgens and nonandrogenic secretions. These data provide further support for a significant role for the Leydig cell in modulating the testicular response to inflammation.
睾丸间质细胞与睾丸的多种炎症相关反应有关。具体而言，这些细胞产生促炎细胞因子白细胞介素-1（IL-1）和IL-6，刺激巨噬细胞募集，并促进间质液形成。此外，免疫调节细胞因子巨噬细胞迁移抑制因子（MIF）、转化生长因子-β1（TGFβ1）和干扰素-γ（IFNγ）由包括睾丸间质细胞在内的睾丸细胞组成性表达。在本研究中，在用睾丸间质细胞特异性毒素乙烷二甲磺酸盐（EDS）处理的成年雄性大鼠中，研究了睾丸间质细胞对睾丸炎症反应的作用。通过皮下植入睾酮来调节睾丸内睾酮水平。10天后，动物接受脂多糖（LPS）注射以诱导炎症反应，或仅注射生理盐水，并在3小时后处死。EDS导致睾丸间质细胞耗竭以及LPS处理均使收集到的睾丸间质液减少至对照水平的约35%，但二者的作用并非相加。维持睾丸内睾酮水平可逆转EDS处理后间质液的减少，并部分预防LPS诱导的效应。MIF、TGFβ1和IFNγ在正常和发炎的睾丸中表达水平相似。相比之下，EDS处理导致这三种细胞因子的表达显著下降，而睾酮植入可预防这种下降。这些数据表明：1）睾丸中TGFβ1、MIF和IFNγ的表达不依赖于完整睾丸间质细胞的存在，而是受睾酮直接控制；2）炎症期间睾丸间质液的减少涉及睾丸间质细胞，其通过雄激素和非雄激素分泌发挥作用。这些数据进一步支持了睾丸间质细胞在调节睾丸对炎症反应中起重要作用的观点。
