Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) blocks the chemotaxis of neutrophils by inhibiting signal transduction through IL-8 receptors.
We investigated the impact of curcumin on neutrophils. Chemotactic activity via human recombinant IL-8 (hrIL-8) was significantly inhibited by curcumin. Curcumin reduced calcium ion flow induced by internalization of the IL-8 receptor. We analyzed flow cytometry to evaluate the status of the IL-8 receptor after curcumin treatment. The change in the distribution of receptors intracellularly and on the cell surface suggested that curcumin may affect the receptor trafficking pathway intracellulary. Rab11 is a low molecular weight G protein associated with the CXCR recycling pathway. Following curcumin treatment, immunoprecipitation studies showed that the IL-8 receptor was associated with larger amounts of active Rab11 than that in control cells. These data suggest that curcumin induces the stacking of the Rab11 vesicle complex with CXCR1 and CXCR2 in the endocytic pathway. The mechanism for antiinflammatory response by curcumin may involve unique regulation of the Rab11 trafficking molecule in recycling of IL-8 receptors.
Takahashi
Masafumi
M
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan.
Ishiko
Takatoshi
T
Kamohara
Hidenobu
H
Hidaka
Hideaki
H
Ikeda
Osamu
O
Ogawa
Michio
M
Baba
Hideo
H
D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D047468:Immunoprecipitation; D016209:Interleukin-8 / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000378:metabolism; D053700:Receptors, Interleukin-8 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D002118:Calcium; D003474:Curcumin; D016209:Interleukin-8; D019707:Receptors, Chemokine; D053700:Receptors, Interleukin-8; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins
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