Role of TNF Alpha, IL-33 and CCL2/MCP-1 in Mast Cell Activity (Pages 35-43)

Pio Conti

Immunology Division, University of Chieti-Pescara, Italy


Abstract: Mast cells are the derivatives of hematopoietic progenitor cells and play an important role in immediate Type I hypersensitivity and late phase reactions but also in innate immunity (3), allergy and inflammation (4) by secreting a large variety of chemical mediators either from storage sites in their granules, or producing immuno-regulatory proteins upon stimulation (5-14). They directly interact with bacteria and appear to play a vital role in host defense against pathogens. The addition of certain cytokines to human umbilical cord blood-derived cultured mast cells shown to augment IgE-induced production of distinct cytokines, without histamine secretion. Mast cells could be recruited in the inflammatory site, by MCP-1, RANTES and SCF, and selectively secrete proinflammatory molecules; these could include growth factors, histamine, which is mitogenic (H1) and an immunosuppressant (H2), neovascularization agents, such as heparin, IL-8, and VEGF as well as proteases that could permit new blood vessel formation.

IL-33 belongs to the IL-1 family and binds to the ST2 receptor which has high homology to IL-1 receptor and has biological activities. IL-33, causes allergic inflammation and exerts significant biological effects both in vivo and in vitro. IL-33 induces expression of several cytokine and chemokine, resulting in severe inflammatory and allergic diseases. Using human umbilical cord blood mast cells (HUCBMCs), as a valid model, we found that IL-33 induces CCL2/MCP-1 release in HUCBMCs. This study documents the ability of IL-33 to directly stimulate HUCBMCs to produce CCL2/MCP-1. We reported that IL-33 is a strong activator of human mast cell capable to induce CCL2/MCP-1 released at translational level. The data described an additional biological activity of IL-33, suggesting that this cytokine may have an important effect on the recruitment of inflammatory cells in allergic diseases. IL-33 may be also critically involved in regulation of cyclooxygenase production in vitro and probably in vivo, providing a potential therapeutic target for inflammatory diseases. CCL2 monocytes chemotactic protein 1 (MCP-1) is a potent chemotactic molecule that attracts lymphocytes, monocytes, mast cells, and memory T cells, but not neutrophils. In this review we highlighted, for the first time, the importance of TNF alpha, IL-33, and MCP-1 in mast cell activity.

Keywords: Mast cell, Chemokine, Cytokine, Inflammation, Immunity.