Presenter: Jonathan Spallino
Authors: Jonathan Spallino, Mary Vallecillo-Zúniga, Peter Poulsen, Jacob Luddington, Christian Arnold, Braden Kartchner
Faculty Advisor: Pam Van Ry
Institution: Brigham Young University
Limb-girdle muscular dystrophy type 2B (LGMD2B) is a progressive disease characterized by the atrophy of skeletal muscle in the shoulder and pelvic girdles. It is caused by a mutation in theDysfgene, which leads to non-functional dysferlin protein. Cells with this mutation are unable to repair damage to the muscle cell membrane, which in turn causes chronic inflammation and an increase in fatty infiltrate within muscles. Galectin-1 (Gal-1) is a promising protein that could be used to treat LGMD2B. We have seen that Gal-1 decreases inflammation and increases muscle membrane repair inin vitroandin vivomodels. We hypothesized that Gal-1 could be reducing inflammation through interactions in the NF-кB pathway. To better understand the effects of Gal-1 on the NF-κB pathway, we wanted to quantify changes in cytokine secretion in dsyferlin-deficient models treated with Gal-1. We cultured A/J-/-myotubes in the presence of .11 μM recombinant human Gal-1 (rHsGal-1) and tested the cell culture media against nontreated culture media using a mouse cytokine profiler. We discovered that IL-4, CXCL-1, MCP-1, and TIMP-2 cytokines were upregulated by 15.5, 1.4, 1.5, and 1.5-fold, respectively. While these cytokines have various functions, all of them either promote tissue regeneration or have anti-inflammatory properties. We confirmed these results by testing cytokine expression in tissue lysates from BLA/J mice treated with either PBS or rHsGal-1. We observed a 38.5-fold increase in IL-4, a 1.9-fold increase in MCP-1, and a 1.4-fold increase in TIMP-2 in mice treated with rHsGal-1 compared to mice treated with PBS. These results suggest that Gal-1 acts on the NF-κB pathway to increase expression of cytokines responsible for decreasing inflammation and promoting tissue regeneration and remodeling.