%0 Journal Article
%T CC-Chemokine CCL15 Expression and Possible Implications for the Pathogenesis of IgE-Related Severe Asthma
%A Yasuo Shimizu
%A Kunio Dobashi
%J Mediators of Inflammation
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/475253
%X Airway inflammation is accompanied by infiltration of inflammatory cells and an abnormal response of airway smooth muscle. These cells secrete chemokines and express the cell surface chemokine receptors that play an important role in the migration and degranulation of inflammatory cells. Omalizumab is a monoclonal antibody directed against immunoglobulin E, and its blocking of IgE signaling not only reduces inflammatory cell infiltration mediated by the Th2 immune response but also inhibits other immune responses. The chemokine CCL15 is influenced by omalizumab, and the source of CCL15 has been reported to be airway smooth muscle cells and basophils. CCL15 binds to its receptor CCR1, which has been reported to be expressed by various inflammatory cells and also by airway smooth muscle cells. Therefore, CCL15/CCR1 signaling could be a target for the treatment of asthma. We review the role of CCL15 in the pathogenesis of asthma and also discuss the influence of IgE-mediated immunomodulation via CCL15 and its receptor CCR1. 1. Introduction Chemokines play an important role in the accumulation of inflammatory cells. They belong to a superfamily of small (6¨C14£¿kDa) proteins that regulate trafficking in various cells [1]. The C-C motif chemokine ligand 15 (CCL15) is a member of the macrophage inflammatory protein-1 family of chemokines, and its gene is located on 17q11.2. The genetic sequence of CCL15 is similar to that of C-C motif chemokine ligand 5 (CCL5) which is known as regulated on activation normal T cell expressed and secreted (RANTES) and C-C motif chemokine ligand 3 (CCL3), which is named macrophage inflammatory protein-1¦Á (MIP-1¦Á). The CCL15 gene has four exons and three introns. CCL15 has also been variously termed macrophage inhibitory protein-5 (MIP-5), leukotactin-1 (Lkn-1), and human C-C chemokine 2 (HCC-2) [2¨C4]. CCL15 binds to two receptors known as CCR1 and CCR3, but it has a higher affinity for the former [2, 5, 6]. Although other chemokines, such as CCL3L1 and CCL5, have already been examined in detail to assess their role in asthma, little is known about the possible influence of CCL15 on asthma. Recently, the serum level of CCL15 was found to be elevated in patients with severe asthma and it was shown to be reduced by omalizumab, a humanized anti-IgE antibody [7]. In addition, airway smooth muscle cells (ASMCs) have been shown to produce CCL15 in vitro, and these cells express CCR1 in asthma patients [8, 9]. This paper reviews the role of CCL15 in the pathogenesis of asthma and also discusses the influence of IgE-mediated
%U http://www.hindawi.com/journals/mi/2012/475253/