Galectin-1 enhances TNF?-induced inflammatory responses in Sertoli cells through activation of MAPK signalling.

ABSTRACT: 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? 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? challenge. Pretreatment with Gal-1 synergistically and specifically enhanced TNF?-induced expression of MCP1, IL-1?, IL-6 and TNF? in Sertoli cells. Combined stimulation of Sertoli cells with Gal-1 and TNF? enhanced the phosphorylation of MAP kinases as compared to TNF? 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? via stimulation of MAPK signalling.

SUBMITTER: Lei T 

PROVIDER: S-EPMC5829165 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other