These findings suggest that TFF3 activates intestinal epithelial cells through G-protein-coupled PAR-2, and could actively participate in the immune system of breastfed babies inducing the production of peptides related to innate defense, such as defensins and cytokines. PARs are activated by the action of serine proteases such as thrombin (acts on PARs 1, 3 and 4) and trypsin (PAR 2). These enzymes cleave the N-terminus of the receptor, which in turn acts as a tethered ligand. In the cleaved state, part of the receptor itself acts as the agonist, causing a physiological response. Most of the PAR family act through the actions of G-proteins i (cAMP inhibitory), 12/13 (Rho and Ras activation) and q (calcium signalling) to cause cellular actions. The cellular effects of thrombin are mediated by protease-activated receptors (PARs). Thrombin signalling in platelets contributes to hemostasis and thrombosis. Endothelial PARs participate in the regulation of vascular tone and permeability while in vascular smooth muscle they mediate contraction, proliferation, and hypertrophy. In endothelial cells PARs play a key role in promotion vascular barrier function as they provide a positive signals for endothelial adhesion molecules (vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1(ICAM-1), and E-selectin). PARs contribute to the pro-inflammatory response. For example PAR4 induces leukocyte migration and PAR2 helps macrophages to produce cytokines such as interleukin-8 (IL-8). Recent research has also implicated these novel receptors in muscle growth and bone cell differentiation and proliferation.