PMID- 11360924
OWN - NLM
STAT- MEDLINE
DCOM- 20010913
LR  - 20191104
IS  - 1567-5769 (Print)
IS  - 1567-5769 (Linking)
VI  - 1
IP  - 2
DP  - 2001 Feb
TI  - Shikonin, a component of antiinflammatory Chinese herbal medicine, selectively 
      blocks chemokine binding to CC chemokine receptor-1.
PG  - 229-36
AB  - 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.
FAU - Chen, X
AU  - Chen X
AD  - Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National 
      Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, 
      USA.
FAU - Oppenheim, J
AU  - Oppenheim J
FAU - Howard, O M
AU  - Howard OM
LA  - eng
GR  - Y2-AT-9002/AT/NCCIH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (CCR1 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokines)
RN  - 0 (Chemokines, CC)
RN  - 0 (Naphthoquinones)
RN  - 0 (Receptors, CCR1)
RN  - 0 (Receptors, Chemokine)
RN  - 3IK6592UBW (shikonin)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Chemokine CCL2/metabolism
MH  - Chemokine CCL5/antagonists & inhibitors/metabolism
MH  - Chemokines/*metabolism
MH  - Chemokines, CC/*metabolism
MH  - Humans
MH  - Naphthoquinones/*pharmacology
MH  - Receptors, CCR1
MH  - Receptors, Chemokine/*drug effects/metabolism
EDAT- 2001/05/22 10:00
MHDA- 2001/09/14 10:01
CRDT- 2001/05/22 10:00
PHST- 2001/05/22 10:00 [pubmed]
PHST- 2001/09/14 10:01 [medline]
PHST- 2001/05/22 10:00 [entrez]
AID - S1567-5769(00)00033-3 [pii]
AID - 10.1016/s1567-5769(00)00033-3 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2001 Feb;1(2):229-36. doi: 10.1016/s1567-5769(00)00033-3.