title: Shikonin, a component of antiinflammatory Chinese herbal medicine, selectively blocks chemokine binding to CC chemokine receptor-1.
abstract: Shikonin is a chemically characterized component of traditional Chinese herbal medicine and has been shown to possess antiinflammatory activities. We ascertained that shikonin blocked radiolabelled Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) and macrophage inflammatory protein-1 (MIP-1alpha) binding to human monocytes with IC50 values of 3.58 x 10(-6) and 2.57 x 10(-6) M, respectively. In contrast, up to 1.7 x 10(-5) M of shikonin failed to inhibit stromal cell-derived factor-1 (SDF-1alpha) binding to the cells. Additionally, shikonin blocked RANTES and MIP-1alpha binding to stable CC chemokine receptor-1 (CCR1) transfected human embryonic kidney (HEK)/293 cells with IC50 values of 2.63 x 10(-6) and 2.57 x 10(-6) M, respectively. However, shikonin inhibited neither RANTES nor MIP-1alpha binding to CCR5 transfected HEK/293 cells. Shikonin also did not inhibit monocyte chemoattractant protein-1 (MCP-1) binding to CCR2 cells, eotaxin binding to CCR3 cells, interferon-inducible T cell alpha-chemoattractant (I-TAC) binding to CXCR3 cells and SDF-1alpha binding to CXCR4 cells. Additionally, shikonin inhibited RANTES-induced CCR1 cell migration, but did not inhibit CCR1 cell migration induced by epidermal growth factor (EGF). Our study suggests shikonin may be a target for the future design of more potent, highly selective therapeutics that could be useful antiinflammatory agents for selectively blocking the binding of CCR1 ligands.
authors.affiliation: Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Oppenheim
authors.forename: O M
authors.initials: OM
authors.lastname: Howard
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism*; D006801:Humans; D009285:Naphthoquinones / Q000494:pharmacology*; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C515300:CCR1 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D009285:Naphthoquinones; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; C016101:shikonin