Eotaxins and CCR3 receptor in inflammatory and allergic skin diseases: therapeutical implications.
Cell migration is mediated by a group of chemotactic cytokines called chemokines: low molecular weight molecules that have been shown as important leukocyte chemical attractants to sites of inflammation and infection. Eotaxin-1, also called CCL11, was first described in 1994, as a highly specific eosinophils chemokine. Many cell types including lymphocytes, macrophages, bronchial smooth muscle cells, endothelial cells and eosinophils, are able to produce this chemokine, predominantly after cytokine stimulation, however little is known about its expression in human skin in vivo. Eotaxin-1 also regulates the chemiotaxis and, in some conditions, activation of basophils, mast cells and T lymphocytes. Chemokine receptors are named from their ligand families, thus the CC chemokine eotaxin-1 binds to the CCR3 receptor which is expressed on eosinophis, mast cells, Th2 type lymphocytes and even on keratinocytes. It seems that eotaxin-1 is one of the most important cytokines involved in tissue inflammation playing a central role in the pathogenesis of allergic airway diseases (asthma and rhinitis), in inflammatory bowel disease and gastrointestinal allergic hypersensitivity and recently it has been proposed as a therapeutical target for these conditions. Our group has studied the role of eotaxin-1 in the pathogenesis of two skin conditions: dermatitis herpetiformis and AIDS-associated eosinophilic folliculitis, demonstrating that this chemokine, together with Th2 type cytokines (IL-13 and IL-4) is important in cell recruitment, inflammation and tissue damage; moreover eotaxin has proven to paly an important role in other skin conditions such as, bullous pemphigoid, pemphigoid gestationis, atopic dermatitis and allergic drug reactions Recent advances in the understanding of eotaxin-1-mediated mechanisms of chemotaxis in allergic and inflammatory conditions may predict that therapeutic antagonism is achievable. This paper will focus on the role that eotaxin and its receptor play in the pathogenetical mechanism in a number of dermatologic diseases, some of which, like atopic dermatitis, may benefit from the introduction of novel and more selective therapeutic options.
Amerio
Paolo
P
Department of Immunodermatology and Allergology, Istituto Dermopatico dell' Immacolata-IRCCS, Rome, Italy. p.amerio@idi.it
Frezzolini
Alessandra
A
Feliciani
Claudio
C
Verdolini
Roberto
R
Teofoli
Patrizia
P
De Pità
Ornella
O
Puddu
Pietro
P
D000818:Animals; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000502:physiology*; D003872:Dermatitis / Q000276:immunology* / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000378:metabolism; D006801:Humans; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000502:physiology*
C515456:CCL11 protein, human; C515484:CCL24 protein, human; C120429:CCL26 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D054397:Receptors, CCR3; D019707:Receptors, Chemokine