Stanniocalcin-1 attenuates ischemic cardiac injury and response of differentiating monocytes/macrophages to inflammatory stimuli

Abstract

Stanniocalcin-1 (STC-1) is a multifunctional glycoprotein with anti-oxidant and anti-inflammatory properties. Ischemic myocardial necrosis generates ‘danger’ signals that perpetuate detrimental inflammatory reactions often involving monocyte recruitment and their subsequent differentiation into pro-inflammatory macrophages. Therefore, we evaluated the effects of recombinant STC-1 (rSTC-1) on monocyte phenotype and in a mouse model of myocardial infarction. Using an established protocol to differentiate human monocytes into macrophages, we demonstrated that rSTC-1 did not alter morphology of the differentiated cells, toll-like receptor (TLR) 4 expression, or expression of the myeloid cell marker CD11b. However rSTC-1 treatment prior to differentiation attenuated the rise in expression of CD14, a TLR4 co-receptor and pathogen sensor that propagates innate immune responses, and suppressed levels of inflammatory cytokines produced by the differentiated cells in response to the TLR4/CD14 ligand lipopolysaccharide (LPS). Moreover, rSTC-1 treatment reduced CD14 expression in monocytes stimulated with endogenous danger signals. Interestingly, the effects of rSTC-1 on CD14 expression were not reproduced by a superoxide dismutase mimetic. In mice with induced myocardial infarcts, intravenous administration of rSTC-1 decreased CD14 expression in the heart as well as levels of TNFα, CXCL2, IL-1β and myeloperoxidase (MPO). It also suppressed formation of scar tissue while enhancing cardiac function. The data suggests that one of the beneficial effects of STC-1 might be attributed to suppression of CD14 on recruited monocytes/macrophages that limits their inflammatory response. STC-1 may be a promising therapy to protect the heart and other tissues from ischemic injury.

Therapeutic potential of products derived from mesenchymal stem/stromal cells in pulmonary disease

“…Preconditioning MSCs under 95% O 2 improved therapeutic benefits of the CM compared with control MSC-CM or lung fibroblast-CM. Correlatively, the preconditioned MSC-CM was also shown to contain a higher amount of STC-1 [ 87 ], which is a pleiotropic protein with antioxidant, anti-apoptotic, and anti-inflammatory potential [ 37 , 88 – 90 ].…”

Regulation of stanniocalcin‐1 secretion by BeWo cells and first trimester human placental tissue from normal pregnancies and those at increased risk of developing preeclampsia

“…STC‐1 has been implicated in a spectrum of biological processes including cell migration, apoptosis, and oxidative phosphorylation. It has anti‐inflammatory properties and acts as a calcium channel blocker in the heart . STC‐1 is present in the serum of healthy pregnant but not non‐pregnant women and is further elevated in pregnancies complicated by preeclampsia .…”

Cornea-Derived Mesenchymal Stromal Cells Therapeutically Modulate Macrophage Immunophenotype and Angiogenic Function

“…Overall, this study advances our understanding of the mechanisms by which cMSCs modulate macrophages and specifically adds PEDF to the list of important mediators (such as TSG‐6, stanniocalcin 1, and prostaglandin E2) which MSCs secrete to modulate macrophages . It will be interesting to further examine the role of PEDF in mediating the therapeutic effects of MSCs from other source including the bone marrow.…”