title: The effects of cigarette smoke extract on the endothelial production of soluble intercellular adhesion molecule-1 are mediated through macrophages, possibly by inducing TNF-alpha release.
abstract: Cigarette smoke (CS) is a major risk factor for many human diseases, although the underlying mechanisms are not clearly understood. This study was undertaken to investigate the effect of a water-soluble CS extract (CSE) on soluble intercellular adhesion molecule-1 (sICAM-1) production by human umbilical vein endothelial cells (HUVEC) mediated through ANA-1 macrophages. First, macrophages were incubated with or without CSE, and the supernatants collected at different time points were used to measure the levels of tumor necrosis factor-alpha (TNF-alpha) and sICAM-1 by enzyme-linked immunosorbent assay (ELISA); and second, HUVEC were cultured with CSE, a vehicle, or ANA-1 supernatants (collected at different time points) and the sICAM-1 levels in the supernatants were measured by ELISA at 24 h. The results showed that: i) CSE showed no effect on the production of sICAM-1 by HUVEC; ii) sICAM-1, in unstimulated or CSE-stimulated ANA-1 supernatants collected at different time points, was under the detectable level; iii) CSE-stimulated ANA-1 supernatants collected at 3 or 6 h showed no effect on sICAM-1 production in HUVEC, while those collected at 12 and 24 h significantly increased sICAM-1 production (p < 0.02 and p < 0.005, respectively); iv) no significant difference in TNF-alpha levels was detected between unstimulated and CSE-stimulated macrophage supernatants collected at 3 and 6 h, however, higher levels of TNF-alpha were found in CSE-stimulated supernatants collected at 12 and 24 h (p < 0.05 and p < 0.002, respectively); and v) a significant correlation (r = 0.9693, p < 0.001) was found between the levels of TNF-alpha in CSE-stimulated ANA-1 supernatants and those of related sICAM-1 production in HUVEC. These findings indicate that CSE indirectly increases the production of sICAM-1 in HUVEC by activating macrophages, which possibly induces the release of TNF-alpha from them, which in turn enhances the production of sICAM-1 from HUVEC.
authors.affiliation: Laboratory of Molecular Biology, 1st Hospital, Taiyuan, P.R. China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Guo
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: Z
authors.initials: Z
authors.lastname: Qiao
authors.forename: J
authors.initials: J
authors.lastname: Qiao
mesh_terms: D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism
chemical_list: D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1