Expression of functional Toll-like receptors 2 and 4 in human aortic valve interstitial cells: potential roles in aortic valve inflammation and stenosis
| Autor: | Charles A. Dinarello, Xiaoping Yang, David A. Fullerton, Joseph C. Cleveland, Ashok N. Babu, Lihua Ao, Maorong Wang, Yong Song, Michael J. Weyant, Xianzhong Meng |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Lipopolysaccharides
Aortic valve medicine.medical_specialty Physiology medicine.medical_treatment Bone Morphogenetic Protein 2 Core Binding Factor Alpha 1 Subunit Inflammation Peptidoglycan Biology Interstitial cell Valve replacement Transforming Growth Factor beta Internal medicine medicine Humans Cells Cultured Interleukin-6 Interleukin-8 NF-kappa B Calcinosis Calcific aortic valve stenosis Aortic Valve Stenosis Cell Biology Intercellular Adhesion Molecule-1 medicine.disease Immunity Innate Toll-Like Receptor 2 Up-Regulation Surgery Toll-Like Receptor 4 Stenosis medicine.anatomical_structure Cytokine Aortic Valve Bone Morphogenetic Proteins Cardiology lipids (amino acids peptides and proteins) medicine.symptom Aortic valve calcification Signal Transduction |
| Zdroj: | American Journal of Physiology-Cell Physiology. 294:C29-C35 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00137.2007 |
| Popis: | Calcific aortic valve stenosis is the most common indication for surgical valve replacement. Inflammation appears to be one of the mechanisms involved in aortic valve calcification, and valve interstitial cells seem to contribute to that process. Although Toll-like receptors (TLRs) play an important role in the cellular inflammatory response, it is unknown whether human aortic valve interstitial cells (HAVICs) express functional TLRs. We examined the expression of TLR2 and TLR4 in human aortic valve leaflets and in isolated HAVICs and analyzed the response of cultured HAVICs to the TLR2 and TLR4 agonists peptidoglycan (PGN) and LPS. Abundant TLR2 and TLR4 proteins were found in human aortic valve leaflets and in isolated HAVICs, and both receptors were detected in the membrane and cytoplasm of cultured HAVICs. Stimulation by either PGN or LPS resulted in the activation of the NF-κB signaling pathway and the production of multiple proinflammatory mediators, including IL-6, IL-8, and ICAM-1. In addition, stimulation by either PGN or LPS upregulated the expression of bone morphogenetic protein-2 (BMP-2) and Runx2, factors associated with osteogenesis. This study demonstrates for the first time that HAVICs express TLR2 and TLR4 and that stimulation of HAVICs by PGN or LPS induces the expression of proinflammatory mediators and the upregulation of osteogenesis-associated factors. These results suggest that TLR2 and TLR4 may play a role in aortic valve inflammation and stenosis. |
| Databáze: | OpenAIRE |
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