Role for neutral sphingomyelinase-2 in tumor necrosis factor alpha-stimulated expression of vascular cell adhesion molecule-1 (VCAM) and intercellular adhesion molecule-1 (ICAM) in lung epithelial cells: p38 MAPK is an upstream regulator of nSMase2.
J Biol Chem
; 282(2): 1384-96, 2007 Jan 12.
Article
in En
| MEDLINE
| ID: mdl-17085432
ABSTRACT
Neutral sphingomyelinases (N-SMases) are major candidates for stress-induced ceramide production. However, there is little information on the physiological regulation and roles of the cloned N-SMase enzyme, nSMase2. In this study, nSMase2 was found to translocate acutely to the plasma membrane of A549 epithelial cells in response to tumor necrosis factor alpha (TNF-alpha) in a time- and dose-dependent manner. Additionally, TNF-alpha increased N-SMase activity rapidly and transiently both endogenously and in cells overexpressing nSMase2. Furthermore, the translocation of nSMase2 was regulated by p38-alpha MAPK, but not ERK or JNK, and the increase in endogenous N-SMase activity was abrogated by p38 MAPK inhibition. In addition, both p38-alpha MAPK and nSMase2 were implicated in the TNF-alpha-stimulated up-regulation of the adhesion proteins vascular cell adhesion molecule-1 (VCAM) and intercellular adhesion molecule-1 (ICAM), but this was largely independent of NF-kappaB activation. These data reveal p38 MAPK as an upstream regulator of nSMase2 and indicate a role for nSMase2 in pro-inflammatory responses induced by TNF-alpha as a regulator of adhesion proteins.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sphingomyelin Phosphodiesterase
/
Tumor Necrosis Factor-alpha
/
Intercellular Adhesion Molecule-1
/
Vascular Cell Adhesion Molecule-1
/
Respiratory Mucosa
/
P38 Mitogen-Activated Protein Kinases
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2007
Type:
Article
Affiliation country:
United States