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Environmental aldehyde, acrolein regulates endothelial cell adhesion molecules
Author(s) -
Sithu Srinivas D,
Srivastava Sanjay,
Vladykovskaya Ele,
Bhatnagar Aruni,
D'Souza Stanley E
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a128
Subject(s) - acrolein , chemistry , cell adhesion molecule , icam 1 , cytokine , cell adhesion , biochemistry , hexanal , inflammation , tumor necrosis factor alpha , immunology , biology , cell , intracellular , organic chemistry , catalysis
Acrolein is a toxic aldehyde, generated during combustion of fossil fuels. It is also generated endogenously during lipid peroxidation. Adhesion molecules ICAM‐1 and VCAM‐1 that are expressed on EC upon cytokine stimulation facilitate leukocyte adhesion and migration during inflammation. In inflammatory diseases, the ectodomain cleavage of these adhesion molecules becomes augmented releasing soluble ICAM‐1 (sICAM‐1) and VCAM‐1 (sVCAM‐1) in the plasma. Mice exposed to acrolein (5 mg/kg by gavage) showed a significant (36 ±2%, P<0.001) reduction in the plasma levels of sICAM‐1, 4h after the exposure that persisted up to 24h (20±1%, P<0.001) when compared with water fed controls. Human ECs were exposed to 0–10 μM acrolein for 1h in media without serum, allowed to recover for 24h and then stimulated with the cytokine, TNF‐α for 16h. The released sICAM‐1 and sVCAM‐1 in the media were measured by ELISA. The results showed a dose‐dependent reduction in the levels of sICAM‐1 (2–32%) and sVCAM‐1 (17–63%). In such studies, JNK phosphorylation was diminished, but ERK 1/2 and p38 were unaffected. As a result of more surface adhesion molecule (due to less cleavage) in acrolein exposed ECs, monocyte adhesion was augmented (1.3–1.4 fold). Acrolein did not affect sICAM‐1 release in EC, virally transfected with ICAM‐1 (in the absence of cytokine). We have reported earlier that ICAM‐1 cleavage is mediated by TNF‐α converting enzyme (TACE) belonging to the matrix metalloproteinase (MMP) family ( J. Biol Chem . 2006; 281 :). Expression of TACE mRNA (but not the levels of endogenous MMP inhibitors, TIMP‐1, −2 and −3) and protein levels were decreased in acrolein exposed EC. The results indicate that acrolein downregulates TACE, modulates cytokine mediated cleavage of ICAM‐1 and VCAM‐1 and augments leukocyte adhesion to the endothelium.