Disease relevance of CCL11

• The apoptotic action of eotaxin/CCL11 suggests a therapeutic modality in the treatment of B cell lymphoma [1].
• In conclusion, these observations suggest that, by activating intracellular TLR3 in BSMC, respiratory RNA virus infections stimulate the production of CCL11 and enhance eosinophilic inflammation of the airways in the Th2-dominant microenvironment [2].
• Threonine for alanine substitution in the eotaxin (CCL11) gene and the risk of incident myocardial infarction [3].
• The chemokine eotaxin (CCL11) is a key player in the trafficking of eosinophils to normal tissues and in the tissue eosinophilia associated with human allergic disease [4].
• Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation [5].
• We conclude that CCL11 signaling plays an important role in proliferation and invasion of ovarian carcinoma cells and CCL11 pathway could be targeted for therapy in ovarian cancer [6].

High impact information on CCL11

• The molecular steps involved in eosinophil development and trafficking are described, with special attention to the important role of the transcription factor GATA-1, the eosinophil-selective cytokine IL-5, and the eotaxin subfamily of chemokines [7].
• CCR3 facilitated infection by a more restricted subset of primary viruses, and binding of the CCR3 ligand, eotaxin, inhibited infection by these isolates [8].
• In addition, a factor chemotactic for human eosinophils with the size and charge characteristics of the eosinophil chemotactic factor of anaphylaxis was identified in blullous fluid [9].
• Blood specimens were obtained from each arm serially over a one-hour interval, and serum speciments were assessed for histamine, eosinophil chemotactic factor of anaphylaxis, and complement components [10].
• This initial observation of release of eosinophil chemotactic factor of anaphylaxis in vivo along with histamine assigns the mast cell a central role in cold urticaria [10].

Chemical compound and disease context of CCL11

• Therefore, pertussis toxin-sensitive Gi-proteins, protein kinase C, tyrosine kinase, phosphatidylinositol-3-kinase and transient increases in [Ca2+]i are involved in the signal transduction of eosinophils following stimulation with eotaxin [11].
• The steroid also reduced eosinophilia in peripheral blood resulting from systemic eotaxin administration (5 microg, i.v.). 7. These data suggest differences in rat CCR3 relative to other species as surmised from a distinctive rank order of chemokine potency [12].
• Role of Eotaxin-1 (CCL11) and CC chemokine receptor 3 (CCR3) in bleomycin-induced lung injury and fibrosis [13].
• Eosinophil shape change in response to eotaxin was inhibited by pertussis toxin, but indomethacin- and PGD(2)-induced shape change responses were not [14].
• To study mechanisms of progenitor cell mobilization in allergic reactions, we investigated fluctuations in the expression of the eotaxin receptor, CC chemokine receptor 3 (CCR3), on CD34+ cells from stable asthmatics following allergen (i.e. antigen) challenge [15].

Biological context of CCL11

• Here we report that another CC chemokine, eotaxin (also known as CCL11), also induced chemotaxis of human microvascular endothelial cells [16].
• CCL11 induced the up-regulation of several profibrogenic molecules such as fibroblast growth factor 1 and 5 and of several CC and CXC chemokines [17].
• Furthermore, transfection studies using a luciferase-driven reporter construct containing eotaxin-1/CCL11 proximal promoter showed that IL-17A induced eotaxin-1/CCL11 at the transcriptional level [18].
• This suggests that CCL11 may contribute to angiogenesis in conditions characterized by increased CCL11 production and eosinophil infiltration such as Hodgkin's lymphoma, nasal polyposis, endometriosis, and allergic diathesis [16].
• OBJECTIVE: To evaluate 9 common CCL11 single nucleotide polymorphisms (SNPs) in nuclear families ascertained through patients with asthma participating in the Childhood Asthma Management Program study [19].

Anatomical context of CCL11

• Because the rat aortic sprouting assay, which is not infiltrated by eosinophils, yielded a positive response to CCL11, this angiogenic response appears to be direct and is not mediated by eosinophil products [16].
• The angiogenic response induced by CCL11 was about one-half of that induced by basic fibroblast factor, and it was accompanied by an inflammatory infiltrate, which consisted predominantly of eosinophils [16].
• TLR3-Mediated Synthesis and Release of Eotaxin-1/CCL11 from Human Bronchial Smooth Muscle Cells Stimulated with Double-Stranded RNA [2].
• The chemotactic activity was consistent with the expression of CCR3, the receptor for CCL11, on human microvascular endothelial cells and was inhibited by mAbs to either human CCL11 or human CCR3 [16].
• CCL11 also induced the formation of blood vessels in vivo as assessed by the chick chorioallantoic membrane and Matrigel plug assays [16].

Associations of CCL11 with chemical compounds

• Moreover, IL-17A significantly induced eotaxin-1/CCL11 release and mRNA expression, an effect that was abrogated with cycloheximide and actinomycin D treatment [18].
• Heterodimerization between CCL2 and CCL11 was also enhanced in the presence of Arixtra [20].
• CCL24 challenge significantly accelerated epithelial wound closure, with similar effects exerted by CCL11 and CCL26 [17].
• Heparin inhibited intracellular calcium flux, respiratory burst and chemotactic responses of eosinophils to CCL11, but not to the chemoattractant C5a, and inhibited binding of CCL11 to CCR3 [21].
• Following treatment with the sulfation inhibitor chlorate or proteoglycanases, no inhibition of CCL11-induced activity was observed using either eosinophils or a CCR3-expressing transfectant cell line [21].

Physical interactions of CCL11

• This study shows that eotaxin also interacts with CCR2 and CCR5 and can, thus, affect the responses of monocytes, which express both receptors [22].
• 125I-Eotaxin-2 binds with high affinity to eosinophils and both eotaxin and cold eotaxin-2 displace the ligand with equal affinity [23].
• IFN-gamma did not influence the TNF-alpha-induced binding of nuclear factor kappaB to a DNA probe derived from the eotaxin promoter [24].
• Eotaxin binds the CC chemokine receptor CCR3 that is highly expressed by eosinophils, and it is considered important in the pathology of chronic respiratory disorders such as asthma [25].
• Eotaxin induces a sustained reduction in the functional adhesive state of very late antigen 4 for the connecting segment 1 region of fibronectin [26].

Enzymatic interactions of CCL11

• In this study we demonstrate that eotaxin is efficiently cleaved by CD26/DPP IV and that the NH2-terminal truncation affects its biological activity [27].

Regulatory relationships of CCL11

• Binding studies showed that eotaxin displaces (125) I-MCP-1 from monocytes in a concentration-dependent manner, and functional experiments showed that eotaxin inhibits MCP-1-induced chemotaxis and enzyme release [22].
• In agreement with this observation, eotaxin induced internalization of CCR5 but not of CCR2 in human monocytes and transfected cells [22].
• Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases [28].
• PD98 059 and SB202 190 both caused inhibition of eotaxin-induced ECP release and chemotaxis [28].
• In addition, HIV-2 infection of CC chemokine receptor 3-transfected cells was inhibited to a similar extent by eotaxin and eotaxin(3-74) [27].

Other interactions of CCL11

• Although there is a mounting body of evidence that eosinophils are recruited to sites of allergic inflammation by a number of beta-chemokines, particularly eotaxin and RANTES, the receptor that mediates these actions has not been identified [29].
• It shares receptors with eotaxin and shows full cross-desensitization with this cosinophil-selective chemokine [30].
• In all assays, eotaxin-2 had the same efficacy as eotaxin, but was somewhat less potent [31].
• MCP-4 shares the pyroglutamic acidproline NH2-terminal motif and 56-61% sequence identity with the three known monocyte chemotactic proteins and is 60% identical to eotaxin [30].
• It has marked functional similarities to MCP-3 and eotaxin [30].

Analytical, diagnostic and therapeutic context of CCL11

• CCR3 ligand eotaxin/CCL11 was detected in lesional skin of CD30(+) CTCL by immunohistochemistry, preferentially in tumor cells [32].
• Eotaxin/CCL11 expression in tumor cells was confirmed by intracellular immunofluorescence [32].
• Furthermore, oral administration of YM-355179 (1 mg/kg) inhibited CCL11-induced shape change of whole blood eosinophils in cynomolgus monkeys [33].
• Intravenous injection of YM-355179 (1 mg/kg) also inhibited eosinophil infiltration into airways of cynomolgus monkeys after segmental bronchoprovocation with CCL11 [33].
• Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils [34].

References