Cocaine inhibits human endothelial cell IL-8 production: the role of transforming growth factor-beta.
Cocaine use is associated with modulation of a broad range of biological functions including the capacity to influence cytokine production in murine and human immunoeffector cells. Little is known, however, regarding the effects of cocaine on endothelial cell cytokine production. Because the vascular endothelium actively participates in acute and chronic inflammatory responses and interleukin-8 (IL-8) is one of the key cytokines involved in the inflammatory process, modification of the production of IL-8 by vascular endothelial cells may interfere with the host response to infection or tissue injury. We investigated the effect of cocaine on endothelial cell IL-8 production. Conditioned supernatant from EA.hy 926 cells were evaluated by ELISA following in vitro cocaine exposure. Cocaine decreased IL-8 production in a dose-responsive manner, and this reduction correlated with down-regulation of IL-8 mRNA expression. Cocaine also increased the production of TGF-beta by EA.hy 926 cells and anti-TGF-beta abrogated the cocaine-mediated decrement of IL-8 production, indicating that cocaine down-regulates endothelial IL-8 production by increasing TGF-beta. Our findings suggest that the immunomodulatory effects of cocaine may be mediated, in part, by modification of endothelial-derived cytokine production.
Mao
J T
JT
Division of Pulmonary and Critical Care Medicine, UCLA School of Medicine and WLA VA, Los Angeles, California, 90073, USA.
Zhu
L X
LX
Sharma
S
S
Chen
K
K
Huang
M
M
Santiago
S J
SJ
Gulsurd
J
J
Tashkin
D P
DP
Dubinett
S M
SM
D002460:Cell Line; D003042:Cocaine / Q000494:pharmacology*; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D016209:Interleukin-8; D016212:Transforming Growth Factor beta; D014662:Vasoconstrictor Agents; D003042:Cocaine