Regulatory effects of deoxycholic acid, a component of the anti-inflammatory traditional Chinese medicine Niuhuang, on human leukocyte response to chemoattractants.
Niuhuang is a commonly used Chinese traditional medicine with immunoregulatory and anti-inflammatory properties. Deoxycholic acid (DCA) is a major active constituent of Niuhuang. The reaction of human leukocytes to chemoattractants is an important part of the host immune response and also plays a crucial role in the development of inflammation. We, therefore, investigated the in vitro effects of DCA on human monocyte and neutrophil responses to classic chemoattractants [fMet-Leu-Phe (fMLP), complement fraction 5a (C5a)], CC chemokine [monocyte chemoattractant protein-1 (MCP-1/CCL2)], and/or CXC chemokines [stromal cell-derived factor-1 (SDF-1alpha/CXCL12), interleukin-8 (IL-8/CXCL8)]. The results showed that DCA significantly inhibited fMLP-induced monocyte and neutrophil chemotaxis and calcium mobilization, and also blocked the binding of [3H]fMLP and anti-formyl peptide receptor (FPR) monoclonal antibodies (mAb) to the cells. The inhibitory effects of DCA on calcium mobilization and anti-FPR-mAb binding to the receptor could be abrogated by washing DCA out of the cell suspension, suggesting that DCA blocked fMLP receptors via a steric hindrance mechanism, not via receptor internalization. DCA had no significant inhibitory effects on MCP-1-, SDF-1alpha-, or C5a-induced monocyte function, or C5a- or IL-8-induced neutrophil function. Taken together, our experimental results suggest that blockade of fMLP receptors may contribute to the anti-inflammatory effects of traditional medicine containing DCA.
Chen
Xin
X
The Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute-Frederick, Bldg. 560, Rm. 31-19, Frederick, MD 21702-1201, USA.
Mellon
Richard Daniel
RD
Yang
Lu
L
Dong
Huifang
H
Oppenheim
Joost J
JJ
Howard
Ola Mae Zack
OM
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000906:Antibodies / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D019069:Cell Respiration / Q000187:drug effects; D018925:Chemokines / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008516:Medicine, Chinese Traditional; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000276:immunology / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000276:immunology / Q000378:metabolism; D018000:Receptors, Peptide / Q000276:immunology / Q000378:metabolism; D014316:Tritium
D000893:Anti-Inflammatory Agents; D000906:Antibodies; D018925:Chemokines; D002630:Chemotactic Factors; D016209:Interleukin-8; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D018000:Receptors, Peptide; D003840:Deoxycholic Acid; D014316:Tritium; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium