Abstract
Histone acetylation regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) plays a critical role in the expression of inflammatory genes, such as vascular cell adhesion molecule-1 (VCAM-1). Oxidative processes have been shown to induce VCAM-1 expression. Here, we investigated the mechanisms underlying IL-1β-induced VCAM-1 expression in human tracheal smooth muscle cells (HTSMCs). Our results showed that IL-1β enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCα (Gö6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-κB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-l-cysteine (NAC)] or transfection with siRNAs of MyD88, PKCα, Src, p47phox, p300, and HDAC4. Moreover, IL-1β stimulated NF-κB and CaMKII phosphorylation through MyD88-dependent PI-PLC/PKCα/c-Src/ROS and PI-PLC/Ca2+/CaM pathways, respectively. Activation of NF-κB and CaMKII may eventually lead to the acetylation of histone residues and phosphorylation of histone deacetylases. These findings suggested that IL-1β induced VCAM-1 expression via these multiple signaling pathways in HTSMCs. Blockade of these pathways may reduce monocyte adhesion via VCAM-1 suppression and attenuation of the inflammatory responses in airway diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 8-21 |
| Number of pages | 14 |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 237 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - May 15 2009 |
| Externally published | Yes |
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Keywords
- Cellular adhesion molecules
- Cytokine
- Histone acetyltransferases
- Histone deacetylases
- NADPH oxidase
ASJC Scopus subject areas
- Toxicology
- Pharmacology
Cite this
Activation of ROS/NF-κB and Ca2+/CaM kinase II are necessary for VCAM-1 induction in IL-1β-treated human tracheal smooth muscle cells. / Luo, Shue Fen; Chang, Chia Chi; Lee, I-Ta; Lee, Chiang Wen; Lin, Wei Ning; Lin, Chih Chung; Yang, Chuen Mao.
In: Toxicology and Applied Pharmacology, Vol. 237, No. 1, 15.05.2009, p. 8-21.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activation of ROS/NF-κB and Ca2+/CaM kinase II are necessary for VCAM-1 induction in IL-1β-treated human tracheal smooth muscle cells
AU - Luo, Shue Fen
AU - Chang, Chia Chi
AU - Lee, I-Ta
AU - Lee, Chiang Wen
AU - Lin, Wei Ning
AU - Lin, Chih Chung
AU - Yang, Chuen Mao
PY - 2009/5/15
Y1 - 2009/5/15
N2 - Histone acetylation regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) plays a critical role in the expression of inflammatory genes, such as vascular cell adhesion molecule-1 (VCAM-1). Oxidative processes have been shown to induce VCAM-1 expression. Here, we investigated the mechanisms underlying IL-1β-induced VCAM-1 expression in human tracheal smooth muscle cells (HTSMCs). Our results showed that IL-1β enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCα (Gö6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-κB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-l-cysteine (NAC)] or transfection with siRNAs of MyD88, PKCα, Src, p47phox, p300, and HDAC4. Moreover, IL-1β stimulated NF-κB and CaMKII phosphorylation through MyD88-dependent PI-PLC/PKCα/c-Src/ROS and PI-PLC/Ca2+/CaM pathways, respectively. Activation of NF-κB and CaMKII may eventually lead to the acetylation of histone residues and phosphorylation of histone deacetylases. These findings suggested that IL-1β induced VCAM-1 expression via these multiple signaling pathways in HTSMCs. Blockade of these pathways may reduce monocyte adhesion via VCAM-1 suppression and attenuation of the inflammatory responses in airway diseases.
AB - Histone acetylation regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) plays a critical role in the expression of inflammatory genes, such as vascular cell adhesion molecule-1 (VCAM-1). Oxidative processes have been shown to induce VCAM-1 expression. Here, we investigated the mechanisms underlying IL-1β-induced VCAM-1 expression in human tracheal smooth muscle cells (HTSMCs). Our results showed that IL-1β enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCα (Gö6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-κB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-l-cysteine (NAC)] or transfection with siRNAs of MyD88, PKCα, Src, p47phox, p300, and HDAC4. Moreover, IL-1β stimulated NF-κB and CaMKII phosphorylation through MyD88-dependent PI-PLC/PKCα/c-Src/ROS and PI-PLC/Ca2+/CaM pathways, respectively. Activation of NF-κB and CaMKII may eventually lead to the acetylation of histone residues and phosphorylation of histone deacetylases. These findings suggested that IL-1β induced VCAM-1 expression via these multiple signaling pathways in HTSMCs. Blockade of these pathways may reduce monocyte adhesion via VCAM-1 suppression and attenuation of the inflammatory responses in airway diseases.
KW - Cellular adhesion molecules
KW - Cytokine
KW - Histone acetyltransferases
KW - Histone deacetylases
KW - NADPH oxidase
UR - http://www.scopus.com/inward/record.url?scp=67349136322&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349136322&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2009.02.025
DO - 10.1016/j.taap.2009.02.025
M3 - Article
C2 - 19281832
AN - SCOPUS:67349136322
VL - 237
SP - 8
EP - 21
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 1
ER -