Fig. 5

Schematic presentation of a model highlighting the probable mode of action of AMA on placental development. Typically, Toll-like receptors (TLRs) mediated action in cytotrophoblasts under the influence of adequate stimuli from decidual cells, T-cells, B-cells, macrophages and NK cells at maternal-fetal interface results in elaboration of a group of cyto/chemokines (CCL2, CCL3, CCL5, CXCL10, IL1, IL6, IL16, IL-2RA, MIF and TNF) which are associated with inflammatory and tolerogenic activities. Substantial evidence suggests that Toll-like receptor signaling pathway involving IL1, IL6, and TNF is critical during early placental development. As shown, many of these cytokines via specific receptors and associated molecules with down-stream engagement of effector moieties (e.g., NF-kB, ERK, MAPK, IP3, DAG and p53) regulate different cellular processes (e.g., inflammatory responses, cell survival, growth, proliferation, migration and apoptosis) on homotypic and heterotypic cells as shown by dashed arrows. The helical peptide like AMA with cationic moieties negatively affects the above-mentioned process at multiple levels as shown by gray arrows. Thus, AMA peptides putatively affect a variety of different cellular outcomes, depending upon the peptide concentrations and the nature of its interactions with cell membranes and membrane proteins, resulting in inadequacy of cellular homeostasis. The cytokines upregulated by AMA are shown in blue italics and down-regulated ones by AMA are shown in red italics. For further details, see the Discussion section and relevant references [12, 19, 21–32, 45–47, 49, 65, 69–71]