Proteoglycans Regulate the Chemotaxis of Dendritic Cells Derived from Human Peripheral Blood Monocytes

Abstract

Dendritic cells (DCs) are a type of antigen-presenting cell which play an essential role in the immune system. The transition from immature DC (iDCs) to mature DCs (mDCs) requires appropriate maturation stimuli, such as pro-inflammatory cytokines or pathogen-derived components. Proteoglycans (PGs), which are composed of core proteins and the glycosaminoglycans that bind to them, are one of the main components of the extracellular matrix around pathogens such as bacteria. This study investigated the effects of PG extracted from the nasal septum cartilage of whale (W-PG) on the maturation of DCs derived from human peripheral blood monocytes. iDCs were prepared from human monocytes using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The iDCs were stimulated by W-PG alone. In another type of experiment, the iDCs were stimulated by MIX (tumor necrosis factor-a a (TNF-a a), IL-1b b, IL-6 and prostaglandin E 2 (PGE 2 )) or a combination of MIX plus W-PG. The stimulation of W-PG alone did not induce the phenotypic maturation from iDCs. However, W-PG promoted the up-regulation of chemokine receptor CCR7-surface expression and the chemotactic responsiveness to CCR7 ligand macrophage inflammatory protein-3b b on MIX-stimulated mDCs although W-PG did not influence matrix metalloproteinase-9 activity which is an important factor in DC migration through the extracellular matrix. The findings that W-PG can selectively regulate the chemotactic activity of DCs in vitro under inflammatory conditions therefore indicate that the interaction of PGs with immune cells including DCs plays an important role in the immune response under the milieu of innate immunity.

Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion

“…Together with prostaglandins, proteoglycans facilitate adhesion and migration and tubulogenesis by primary endothelial cells and promote phosphorylation of signaling molecules such as Akt and Src [94, 197]. Prostaglandins in concert with proteoglycans also promote the recruitment of stromal cells from the bone marrow to the developing tumor microenvironment [198, 199]. These include CXCL12, CXCR4, and S100A4 producing fibroblasts that involve signaling through a COX-2/PGE 2 -EP3/EP4-dependent pathway [199].…”

“…These include CXCL12, CXCR4, and S100A4 producing fibroblasts that involve signaling through a COX-2/PGE 2 -EP3/EP4-dependent pathway [199]. Similarly, the combined effect of prostaglandins and proteoglycans regulates the transition from immature dendritic cells (iDCs) to mature DCs (mDCs) [198]. In breast cancer cells, prostaglandins and proteoglycans stimulate invasion across a basement membrane and induces synthesis of specific heparin-binding splice variants of vascular endothelial cell growth factor (VEGF) [200].…”

A novel composition for in vitro and in vivo regeneration of skin and connective tissues

“…Coupled with basement membranes, it provides a structural network for cell growth . Moreover, extracellular matrix sustains the repair process, binds cells together, provides cushioning and viscosity and serves as a medium for cell migration and diffusion of growth factors and other molecules . A wound is defined as an injury resulting from short term injury at a discrete site .…”

“…Chemotaxis is the process whereby a cell is able to detect chemical extracellular signal gradients and moves in the direction of the concentration gradient . Chemotaxis plays an essential role in development, in the immune system and in tissue regeneration …”

“…In relation to wound healing, it is conceivable to use molecules capable of restoring the physiological microenvironment of a specific tissue and stimulating a correct repair of lesions. The experimental collected data and the literature can become precious indications to find possible therapeutic strategies to wound healing of skin and mucosal and connective tissues without fibrotic reaction …”