Chemokines: CC Subfamily – CCL11 (Eotaxin)

Wednesday, 12/05/2010  |   Chemokines  |  no comments

Chemokines: CC Subfamily – CCL11 (Eotaxin)
Chemokines, a superfamilly of small cytokine-like molecules, regulate leukocyte transport in the body. In recent years, we have witnessed the transition of immunotherapeutic strategies. The role of chemokines in tumour biology and the development of the host’s anti-tumour defence indicate that chemokines have therapeutic potential as adjuvants or treatments in anti-tumour immunotherapy (Homety et al, 2002).

Eotaxin is a potent eosinophil chemoattractant that is a member of the CC chemokine subfamily of inflammatory and immunoregulatory cytokines (R & D Systems). Several CXC family chemokine members induce angiogenesis and promote tumour growth. Here we report that another CC chemokine, eotaxin (also known as CCL11), also induced chemotaxis of human microvascular endothelial cells. CCL11 may contribute to angiogenesis in conditions characterised by increased CCL11 production and eosinophil infiltration such as Hodgkin’s lymphoma, nasal polyposis, asthma, endometriosis, and allergic diathesis (Salcedo et al, 2001).
Circulating levels of CCL11 in sera of patients with ovarian cancer were significantly lower than those in healthy women or women with breast, lung, liver, pancreatic or colon cancers. CCL11 signalling plays an important role in proliferation and invasion of ovarian carcinoma cells and CCL11 pathway could be targeted for therapy in ovarian cancer (Levina et al, 2009).

Botanical Interventions:
Baicalein

Eotaxin is an eosinophil-specific chemokine associated with the recruitment of eosinophils to sites of allergic inflammation. “Saiboku-to” (Formula magnoliae et bupleuri) is a kampo herbal medicine used for the treatment of bronchial asthma in Japan. In this study, we investigated the effects of Scutellaria Root, a major herb in Saiboku-to and its components such as baicalein and baicalin on eotaxin production by IL-4 plus TNF-alpha-stimulated human fibroblasts. An extract of Scutellaria Root markedly inhibited eotaxin production.
Four major flavonoids from Scutellaria Root were found to show inhibitory activity on eotaxin production at a concentration of 10 micrograms/ml in the order of baicalein > oroxylin A > baicalin > skullcapflavon II. The inhibitory effect of baicalein was expressed in a dose-dependent manner, and almost 50% inhibition was observed at 1.8 micrograms/ml. Furthermore, baicalein prevented human eotaxin mRNA expression in IL-4 plus TNF-alpha-stimulated human fibroblasts. These results help explain the pharmacological efficacy of Scutellaria Root in the treatment of bronchial asthma since it would suppress eotaxin associated recruitment of eosinophils (Nakajima et al, 2001).

Triptolide
Objective To study the effects of triptolide on the expression of STAT6 and eotaxin in asthmatic mouse model, and to explore the possible therapeutic mechanism of triptolide in asthma.
Methods: The asthmatic model was established by ovalbumin injection and inhalation. The mice were randomly divided into 7 groups and treated respectively with normal saline (as control), dexamethasone or different dose of triptolide. The number of total leukocytes and eosinophils in branchoalveolar lavage fluid (BALF) was measured by light microscope. The mRNA of STAT6 and eotaxin in lung tissue and the protein expression in airway epithelium were detected by reverse transeription polymerase chain reactin (RT-PCR) and immunohistochemistry respectively.
Results: Eotaxin and STAT6 mRNA in lung tissue and the protein expression in airway epithelium of asthmatic group significantly increased compared with those of control group(PReferences
Homey, B., Müller, A. & Zlotnik, A. Chemokines: agents for the immunotherapy of cancer? Nature Reviews Immunology 2, Pp. 175-84. 2002 doi:10.1038/nri748

Levina, V., Nolen, B.M., Marrangoni, A.M., Cheng, P., Marks, J.R., Szczepanski, M.J., Szajnik, M.E., Gorelik, & Lokshin, A.E. Role of CCL11/eotaxin-1 signalling in ovarian cancer. Clin Cancer Res. 2009 April 15; 15(8): Pp.2647–56.

Nakajima, T., Imanishi, M., Yamamoto, K., Cyong, J.C. & Hirai, K. Inhibitory effect of baicalein, a flavonoid in Scutellaria Root, on eotaxin production by human dermal fibroblasts. Planta Med. 2001 Mar;67(2):Pp.132-5.

R & D Systems. Accessed 05/14/10 http://www.rndsystems.com/molecule_detail.aspx?m=1367

Salcedo, R., Young, H.A., Ponce, M.L., Ward, J.M., Kleinman, H.K., Murphy, W.J. & Oppenheim, J.J. Eotaxin (CCL11) Induces In Vivo Angiogenic Responses by Human CCR3+ Endothelial Cells. The Journal of Immunology, 2001, 166: Pp.7571-78.

Sheng, Q., He, Jian-y., Zhou, A-l. & Lin, X-m. Effects of triptolide on the expression of STAT6 and eotaxin in asthmatic mice. Guo Ji Hu Xi Za Zhi. 2006; 26(1): 12-15.

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