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

Infectious, inflammatory and ‘autoimmune’ male factor infertility: how do rodent models inform clinical practice?

“…Blockade of HMGB1 release by ethyl pyruvate in EAO rats animals reduced disease progression and spermatogenic damage ( Aslani et al , 2015 ). Furthermore, involvement of galectin-1, activins and inhibin in the development of testicular immunopathology is also documented ( Suescun et al , 2001 ; Perez et al , 2015 ; Lei et al , 2017 ; Nicolas et al , 2017a , 2017b ).…”

Molecular and epigenetic pathogenesis of germ cell tumors

“…In a model of rat experimental autoimmune orchitis (EAO), the later pathway was recently acknowledged to activate Galectin-1 (Gal-1) and TNF-α secretion by Sertoli cells. This inflammatory response eventually leads to onset of further cytokines, such as IL-1β and IL-6 [ 68 ]. This pro-inflammatory environment consisting of cytokines, such as IL-1β, IL-6, TNF-α, and chemokines, such as CCL5, SDF-1/CXCL12, and CXCL-13, has been reported in GCNIS and SE [ 69 ], rising the thought of a pro-inflammatory micromilieu being favorable during the development of TGCTs ( Table 1 ).…”

T Lymphocytes and Testicular Immunity: A New Insight into Immune Regulation in Testes

“…Moreover, galectin-1 is expressed in SCs and plays a proinflammatory role through MAPK signaling in the early or acute stage of chronic inflammation. It is also able to promote the differentiation of tolerogenic DCs and Tregs, suggesting the dual role of SCs in testicular immunity [118]. On the other hand, these SC-secreting cytokines, especially TGF-β, can regulate the pluripotency and proliferation of germline and SCs themselves and may therefore impact sperm formation under chronic inflammation stimulation [119].…”