Eotaxins and CCR3 Receptor in Inflammatory and Allergic Skin Diseases: Therapeutical Implications

Abstract

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.

IL-18 cDNA vaccination protects mice from spontaneous lupus-like autoimmune disease

“…IL-18 is a potent activator of polarized Th1 cells and induces IFN-␥ production and lymphocyte proliferation. A correlation between IL-18 and the autoimmune pathology has been suggested in several autoimmune syndromes, such as autoimmune diabetes in mice (21), experimental autoimmune encephalitis in rats and mice (22,23,37), experimental and rheumatoid arthritis (24,25,28,29), human Crohn's disease and ulcerative colitis (26,27,38,39), and human systemic lupus erythematosus (30)(31)(32)(33)35).…”

“…Increased levels of circulating IL-18 also correlate with disease activity in human systemic lupus erythematosus (30)(31)(32)(33). In the lpr lupus-like syndrome lymph node (LN) cells and LN-derived autoreactive T cell lines are hyperreactive to IL-18 in terms of proliferation and IFN-␥ production, possibly because of the constitutive expression of the IL-18 receptor ␤ chain (34).…”

Up-regulation of CCL11 and CCL26 is associated with activated eosinophils in bullous pemphigoid

“…The serum values of CCL11 correlated with the disease severity [20]. CCL11 can be expressed by many cell types including eosinophils, keratinocytes, fibroblasts and macrophages [27]. Its expression is induced by IL-4 in human dermal fibroblasts [12] and by tumour necrosis factor (TNF)-a, IL-1a and interferon (IFN)-g in human umbilical vein endothelial cells (HUVEC) [28].…”

Рівень Сироваткового Еотаксину Як Маркер Тяжкості Атопічного Дерматиту В Дітей Раннього Віку

“…5 лейкотрієни, інтерлейкін-5, еозинофільний катіон-ний протеїн [5][6][7]. У зв'язку з цим актуальним є та-кож вивчення рівнів еотаксину як маркера тяжкості та прогнозу перебігу алергічного запалення [8]. Показано, що кількість еозинофілів у шкірі ко-релює з кількістю клітин, які експресують рецепто-ри до специфічних хемоатракторів (хемокінів) -ео-таксин-1 (CCL11), еотаксин-2 (CCL24), еотаксин-3 (CCL26) [9].…”