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Mechanisms of induction of endothelial cell E-selectin expression by smooth muscle cells and its inhibition by shear stress
| Content Provider | Scilit |
|---|---|
| Author | Chiu, Jeng-Jiann Chen, Li-Jing Lee, Chih-I Lee, Pei-Ling Lee, Ding-Yu Tsai, Min-Chien Lin, Chia-Wen Usami, Shunichi Chien, Shu |
| Copyright Year | 2007 |
| Description | E-selectin is a major adhesion molecule expressed by endothelial cells (ECs), which are exposed to shear stress and neighboring smooth muscle cells (SMCs). We investigated the mechanisms underlying the modulation of EC E-selectin expression by SMCs and shear stress. SMC coculture induced rapid and sustained increases in expression of E-selectin and phosphorylation of interleukin-1 (IL-1) receptor-associated kinase glycoprotein-130, as well as the downstream mitogen-activated protein kinases (MAPKs) and Akt. By using specific inhibitors, dominant-negative mutants, and small interfering RNA, we demonstrated that activations of c-Jun-NH2-terminal kinase (JNK) and p38 of the MAPK pathways are critical for the coculture-induced E-selectin expression. Gel shifting and chromatin immunoprecipitation assays showed that SMC coculture increased the nuclear factor-κB (NF-κB)–promoter binding activity in ECs; inhibition of NF-κB activation by p65-antisense, lactacystin, and N-acetyl-cysteine blocked the coculture-induced E-selectin promoter activity. Protein arrays and blocking assays using neutralizing antibodies demonstrated that IL-1β and IL-6 produced by EC/SMC cocultures are major contributors to the coculture induction of EC signaling and E-selectin expression. Preshearing of ECs at 12 dynes/cm2 inhibited the coculture-induced EC signaling and E-selectin expression. Our findings have elucidated the molecular mechanisms underlying the SMC induction of EC E-selectin expression and the shear stress protection against this SMC induction. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1924488/pdf |
| Ending Page | 528 |
| Page Count | 10 |
| Starting Page | 519 |
| DOI | 10.1182/blood-2006-08-040097 |
| Journal | Blood |
| Issue Number | 2 |
| Volume Number | 110 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2007-07-15 |
| Access Restriction | Open |
| Subject Keyword | Biochemistry and Molecular Biology Molecular Mechanics Interleukin 1 Endothelial Cell Mitogen Activated Protein Kinase E Selectin Anti Body Activator Protein Small Interfering Rna Shear Stress Gene Expression Regulation Signal Transduction Journal: Blood (Vol- 60, Issue- 2) |
| Content Type | Text |
| Resource Type | Article |
