Galectin-1 enhances TNFα-induced inflammatory responses in Sertoli cells through activation of MAPK signalling

Galectin-1 (Gal-1) is a pleiotropic lectin involved in the modulation of immune responses. Using a model of rat experimental autoimmune orchitis (EAO), we investigated the role of Gal-1 in testicular inflammation. EAO is characterized by leukocytic infiltrates in the interstitium, damage of spermatogenesis and production of inflammatory mediators like TNF alpha and MCP1 causing infertility. In normal rat testis Gal-1 was mainly expressed in Sertoli cells and germ cells. In the inflamed testis, Gal-1 expression was significantly downregulated most likely due to germ cell loss. Analyses of lectin binding and expression of glucosaminyl-and sialyltransferases indicated that the glycan composition on the cell surface of Sertoli and peritubular cells becomes less favourable for Gal-1 binding under inflammatory conditions. In primary Sertoli cells Gal-1 expression was found to be upregulated after TNF alpha challenge. Pretreatment with Gal-1 synergistically and specifically enhanced TNF alpha-induced expression of MCP1, IL-1 alpha, IL-6 and TNF alpha in Sertoli cells. Combined stimulation of Sertoli cells with Gal-1 and TNFa enhanced the phosphorylation of MAP kinases as compared to TNF alpha or Gal-1 alone. Taken together, our data show that Gal-1 modulates inflammatory responses in Sertoli cells by enhancing the pro-inflammatory activity of TNF alpha via stimulation of MAPK signalling.