Suppression of Chemokine Gene Expression and Production in LPS-Stimulated Macrophages by a 130 kDa Glycoprotein from Plerocercoids of Spirometra erinaceieuropaei

Previous studies have shown that excretory/secretory (ES) products from plerocercoids of Spirometra erinaceieuropaei have immunosuppressive activities. We report here that a 130 kDa glycoprotein (ES130) purified from ES products as a suppressive factor of nitric oxide synthesis in LPS-stimulated RAW 264.7 cells inhibited the gene expression of 3 chemokines, regulated on activation normal T cell expressed and secreted (CCL5/RANTES), macrophage inflammatory protein 2 (CXCL2/MIP-2), interferon-inducible protein 10 kDa (CXCL10/IP-10) in RAW 264.7 cells and mouse peritoneal macrophages stimulated with LPS for 3 h. These chemokines are important factors for recruitment of inflammatory leukocytes. RANTES acts on monocytes, basophils, lymphocytes, natural killer cells and eosinophils. MIP-2 is a potent chemoattactant for neutrophils, while IP-10 binds to Th1 cells. Nearly 80% of MIP-2 gene expression and 50% of IP-10 gene ex-pression in peritoneal macrophages stimulated with LPS for 8 h was suppressed as well as these chemokine production by the preincubation with 100 ng/mL of ES130 or 5000 ng/mL crude ES products for 24 h. On the other hand the mRNA expression of RANTES in macrophages stimulated with LPS for 8 h or 24 h was not inhibited by ES130 or crude ES products, while the RANTES chemokine levels in the incubation medium were significantly suppressed. These results suggest that ES130 may attenuate inflammation around the plerocercoids by inhibiting these chemokine production.