Role of acylglycerol kinase in LPA-induced IL-8 secretion and transactivation of epidermal growth factor-receptor in human bronchial epithelial cells

Kalari, Satish; Zhao, Yutong; Spannhake, E. W.; Berdyshev, Evgeny; Natarajan, Viswanathan

doi:10.1152/ajplung.90431.2008

Cited by 39 publications

(39 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AGK siRNA transfection attenuated LPA-induced sST2 gene expression (Figure 8C). This result is consistent with our previous finding that intracellular LPA regulates exogenous LPA-induced gene expression through activation of NF-κB and AP-1 pathways [35]. …”

Section: Resultssupporting

confidence: 94%

“…Here, by using Chip experiments, we found that down-regulation of AGK by AGK siRNA transfection (50 nM, 72 h) attenuated LPA-induced histone H3 acetylation on sST2 promoter region (Figure 8A), suggesting a role of intracellular LPA in regulation of histone H3 acetylation and chromatin modification. The effect of AGK siRNA on abrogating AGK expression using real time RT-PCR with human AGK primers has been previously reported [35]. Further, the effect of AGK siRNA on LPA-induced sST2 gene expression was examined.…”

Section: Resultsmentioning

confidence: 98%

“…Our previous study had shown that reduction of intracellular LPA levels by down-regulation of acyl glycerol kinase (AGK) attenuated exogenous LPA-induced NF-κB activation and IL-8 expression in HBEpCs [35]. Here, by using Chip experiments, we found that down-regulation of AGK by AGK siRNA transfection (50 nM, 72 h) attenuated LPA-induced histone H3 acetylation on sST2 promoter region (Figure 8A), suggesting a role of intracellular LPA in regulation of histone H3 acetylation and chromatin modification.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Lysophosphatidic acid increases soluble ST2 expression in mouse lung and human bronchial epithelial cells

Zhao

Chen

et al. 2012

Cellular Signalling

Self Cite

View full text Add to dashboard Cite

Lysophosphatidic acid (LPA), a naturally occurring bioactive lysophospholipid increases the expression of both pro-inflammatory and anti-inflammatory mediators in airway epithelial cells. sST2 Soluble ST2 (sST2), an anti-inflammatory mediator, has been known to function as a decoy receptor of interleukin (IL)-33 and attenuate endotoxin-induced inflammatory responses. Here, we show that. LPA increased sST2 mRNA expression and protein release in a dose and time dependent manner in human bronchial epithelial cells (HBEpCs). LPA receptors antagonist and Gαi inhibitor, pertussis toxin, attenuated LPA-induced sST2 release. Inhibition of NF-κB or JNK pathway reduced LPA-induced sST2 release. LPA treatment decreased histone deacetylase 3 (HDAC3) expression and enhanced acetylation of histone H3 at lysine 9 that binds to the sST2 promoter region. Furthermore, limitation of intracellular LPA generation by the down-regulation of acetyl glycerol kinase attenuated exogenous LPA-induced histone H3 acetylation on sST2 promoter region, as well as sST2 gene expression. Treatment of HBEpCs with recombinant sST2 protein or sST2-rich cell culture media attenuated endotoxin-induced phosphorylation of PKC and airway epithelial barrier disruption. These results unravel a novel sST2 mediated signaling pathway that has physiological relevance to airway inflammation and remodeling.

show abstract

Section: Resultssupporting

confidence: 94%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Lysophosphatidic acid increases soluble ST2 expression in mouse lung and human bronchial epithelial cells

Zhao

Chen

et al. 2012

Cellular Signalling

Self Cite

View full text Add to dashboard Cite

show abstract

“…Phosphatidic acid acts as a second messenger regulating a number of cellular processes [27][28][29] and plays a role in the synthesis of phospholipids. The roles of AGK in the cell can explain the features of cataracts, respiratory chain dysfunction and mitochondrial morphology seen in Sengers patients (Fig.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial citrate synthase crystals: Novel finding in Sengers syndrome caused by acylglycerol kinase (AGK) mutations

Siriwardena

MacKay

Levandovskiy

et al. 2013

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

“…This may be physiologically relevant during inflammatory diseases or during epithelial cell injury when LPA synthesis within the cell may be elevated. It may be noted that mitochondrial LPA, nuclear LPA receptors, and targets of intracellular LPA, namely peroxisomeproliferator-activated receptor ␥, are all highly expressed in the colon and play a key role in bacteria-induced inflammation (30,31). By sequestering LPA, villin could contribute to the host defense and repair response.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Lysophosphatidic Acid and Phosphatidylinositol 4,5-Bisphosphate on Actin Dynamics by Direct Association with the Actin-binding Protein Villin

Tomar

George

Mathew

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

We have previously reported that the epithelial cell-specific actin-binding protein villin directly associates with phosphatidylinositol 4,5-bisphosphate (PIP 2 ) through three binding sites that overlap with actin-binding sites in villin. As a result, association of villin with PIP 2 inhibits actin depolymerization and enhances actin cross-linking by villin. In this study, we demonstrate that these three PIP 2 -binding sites also bind the more hydrophilic phospholipid, lysophosphatidic acid (LPA) but with a higher affinity than PIP 2 (dissociation constant (K d ) of 22 M versus 39.5 M for PIP 2 ). More interestingly, unlike PIP 2 , the association of villin with LPA inhibits all actin regulatory functions of villin. In addition, unlike PIP 2 , LPA dramatically stimulates the tyrosine phosphorylation of villin by c-Src kinase. These studies suggest that in cells, selective interaction of villin with either PIP 2 or LPA could have dramatically different outcomes on actin reorganization as well as phospholipid-regulated cell signaling. These studies provide a novel regulatory mechanism for phospholipid-induced changes in the microfilament structure and cell function and suggest that LPA could be an intracellular regulator of the actin cytoskeleton.Many actin-binding proteins are recruited to the plasma membrane to form lipid-protein interactions during cell signaling, membrane trafficking, and cell migration. Membrane recruitment of these microfilament proteins is mediated by membrane-targeting domains that recognize specific lipid molecules in the membranes (1). Phospholipids are implicated in the regulation of actin dynamics, cell growth, cell differentiation, cell survival, and cell motility (1). Phosphoinositides control the activity of various actin-associated proteins by promoting actin filament assembly and down-regulating actin disassembly at appropriate regions within the cell (1).Villin is an epithelial cell-specific actin-binding protein that regulates actin dynamics, cell morphology, cell migration, and apoptosis ,underscoring the significance of this protein to epithelial cell function (2). Villin belongs to a large family of actinbinding proteins that associate with phospholipids (3). Villin binds PIP 2 2 with a K d of 39.5 M and a stoichiometry of 3, and we have previously identified three PIP 2 -binding domains in villin (3). Association of villin with PIP 2 modifies its actin regulatory functions (3). The association of villin with PIP 2 is also required for the catalytic activation of the other ligand of villin, phospholipase C-␥ 1 (4), which is required for the function of villin in cell migration (5, 6).Lysophosphatidic acid (LPA) and its receptors are found in a wide variety of tissues and cell types, indicating their physiological significance to many biological functions (7). LPA is produced by platelets, fibroblasts, mesothelial cells, and adipocytes, and the physiological role of LPA in innate immunity, reproduction, vascular development, and nervous system functions is well recognized (7)...

show abstract

Role of acylglycerol kinase in LPA-induced IL-8 secretion and transactivation of epidermal growth factor-receptor in human bronchial epithelial cells

Cited by 39 publications

References 43 publications

Lysophosphatidic acid increases soluble ST2 expression in mouse lung and human bronchial epithelial cells

Lysophosphatidic acid increases soluble ST2 expression in mouse lung and human bronchial epithelial cells

Mitochondrial citrate synthase crystals: Novel finding in Sengers syndrome caused by acylglycerol kinase (AGK) mutations

Differential Effects of Lysophosphatidic Acid and Phosphatidylinositol 4,5-Bisphosphate on Actin Dynamics by Direct Association with the Actin-binding Protein Villin

Contact Info

Product

Resources

About