UTP causes interleukin (IL)-6 production via mRNA expression through P2Y(2)/P2Y(4) receptors in human HaCaT keratinocytes. In the present study, we analyzed the mechanism of UTP-induced IL-6 production in these cells. UTP, an agonist of P2Y(2)/P2Y(4) receptors, induced phosphorylation of extracellular signal-regulated kinase (ERK) in a concentration- and time-dependent manner. PD98059, a MEK (mitogen-activated protein kinase kinase) inhibitor, and BAPTA-AM [O,O'-bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester], an intracellular Ca(2+) chelator, reduced UTP-induced ERK phosphorylation and IL-6 mRNA expression. 2-APB [(2-aminoethoxy)diphenylborane], an inositol 1,4,5-trisphosphate (IP(3))-receptor antagonist, inhibited UTP-induced IL-6 mRNA expression; and the action of A23187, a Ca(2+) ionophore, resembled the action of UTP. In contrast, protein kinase C (PKC) downregulation and pertussis toxin did not affect UTP-induced IL-6 mRNA expression, suggesting that PKC and G(i) are not involved in the UTP-induced IL-6 production. However, AG1478, an epidermal growth factor (EGF)-receptor inhibitor, partially decreased UTP-induced ERK phosphorylation and IL-6 expression. These results suggest that UTP-induced IL-6 production is in part mediated via phosphorylation of ERK through G(q/11)/IP(3)/[Ca(2+)](i) and transactivation of the EGF receptor.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1254/jphs.fp0060669 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Carbon Monoxide Inhibits Cytokine and Chloride Secretion in Human Bronchial Epithelia.
Cell Physiol Biochem
September 2018
School of Biomedical Sciences, The Chinese University of Hong Kong, N.T., Hong Kong, China.
Background/aims: Carbon monoxide (CO) is an important gas produced endogenously by heme oxygenase (HO) that functions as an anti-inflammatory and in ion channel modulation, but the effects of CO on airway inflammation and ion transport remains unclear.
Methods: The effect of CO on cell damage- and nucleotide-induced pro-inflammatory cytokine release in primary human bronchial epithelia cells (HBE) and in the 16HBE14o- human bronchial epithelial cell line were investigated. The effects of CO on calcium- and cAMP-dependent chloride (Cl-) secretion were examined using a technique that allowed the simultaneous measurement and quantification of real-time changes in signalling molecules (cAMP and Ca2+) and ion transport in a polarised epithelium.
Cooperation of calcineurin and ERK for UTP-induced IL-6 production in HaCaT keratinocytes.
Eur J Pharmacol
November 2007
Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
UTP causes IL-6 production in HaCaT keratinocytes, which is partially inhibited by PD98059, a mitogen-activated protein kinase kinase (MEK) inhibitor, suggesting that a pathway other than the extracellular signal-regulated kinase (ERK) pathway is involved in the production. In the present study, we examined the involvement of calcineurin in the UTP-induced interleukin (IL)-6 production in HaCaT keratinocytes. FK506 and cyclosporine A, calcineurin inhibitors, partially inhibited UTP-induced IL-6 mRNA expression and protein production.
View Article and Find Full Text PDFContribution of extracellular signal-regulated kinase to UTP-induced interleukin-6 biosynthesis in HaCaT keratinocytes.
J Pharmacol Sci
December 2006
Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Sendai, Japan.
UTP causes interleukin (IL)-6 production via mRNA expression through P2Y(2)/P2Y(4) receptors in human HaCaT keratinocytes. In the present study, we analyzed the mechanism of UTP-induced IL-6 production in these cells. UTP, an agonist of P2Y(2)/P2Y(4) receptors, induced phosphorylation of extracellular signal-regulated kinase (ERK) in a concentration- and time-dependent manner.
View Article and Find Full Text PDFPotentiation of lipopolysaccharide-induced IL-6 release by uridine triphosphate in macrophages: cross-interaction with cyclooxygenase-2-dependent prostaglandin E(2) production.
J Biomed Sci
December 1999
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Our previous study has demonstrated the potentiation by uridine triphosphate (UTP) of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in lipopolysaccharide (LPS)-stimulated murine J774 macrophages. In this study, we found that the amount of interleukin-6 (IL-6) release in response to LPS stimulation was greatly enhanced in the presence of UTP. This enhancement exhibited concentration dependence and occurred after 8 h of treatment with LPS.
View Article and Find Full Text PDFInhibition of protein N-glycosylation by 2-deoxy-2-fluoro-D-galactose.
Biochem J
August 1992
Medizinische Universitätsklinik, Albert-Ludwigs-Universität, Freiburg, Germany.
The effects of 2-deoxy-2-fluoro-D-galactose (dGalF) on N- and O-glycosylation of proteins was studied in rat hepatocyte primary cultures and in human monocytes. In hepatocytes, dGalF at concentrations of 1 mM or higher completely inhibited N-glycosylation of alpha 1-antitrypsin and alpha 1-acid glycoprotein, whereas 4 mM-2-deoxy-D-galactose (dGal) only slightly impaired N-glycosylation. In monocytes, 1 mM- or 4 mM-dGalF blocked N-glycosylation of alpha 1-antitrypsin and of interleukin-6, while O-glycosylation of interleukin-6 remained unaffected.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!