TL1A induces the expression of TGF-β-inducible gene h3 (βig-h3) through PKC, PI3K, and ERK in THP-1 cells

Seung Hee Lee, Eun Ju Kim, Kyoungho Suk, In-San Kim, Won Ha Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

βig-h3, an extracellular matrix protein involved in various biological processes including cellular growth, differentiation, adhesion, migration, and angiogenesis, has been shown to be elevated in various inflammatory processes. Death receptor 3 (DR3), a member of the TNF-receptor superfamily that is expressed on T cells and macrophages, is involved in the regulation of inflammatory processes through interaction with its cognate ligand, TNF-like ligand 1A (TL1A). In order to find out whether the TL1A-induced inflammatory activation of macrophages is associated with the up-regulation of βig-h3 expression, the human acute monocytic leukemia cell line (THP-1) was stimulated with either recombinant human TL1A- or DR3-specific monoclonal antibodies. Stimulation of DR3 up-regulated the intracellular levels as well as the secretion of βig-h3. Utilization of various inhibitors and Western blot analysis revealed that activation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), phosphoinositide kinase-3 (PI3K), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is required for TL1A-induced βig-h3 expression. PKC appears to be the upstream regulator of PI3K since the presence of PKC inhibitor blocked the phosphorylation of AKT without affecting ERK phosphorylation. On the other hand, suppression of either PI3K or ERK activity resulted in the suppression of IκB phosphorylation. These findings indicate that TL1A can regulate the inflammatory processes through modulation of the βig-h3 expression through two separate pathways, one through PKC and PI3K and the other through ERK, which culminates at NF-κB activation.

Original languageEnglish
Pages (from-to)61-66
Number of pages6
JournalCellular Immunology
Volume266
Issue number1
DOIs
Publication statusPublished - 2010 Sep 21
Externally publishedYes

Fingerprint

Extracellular Signal-Regulated MAP Kinases
Phosphatidylinositol 3-Kinases
Protein Kinase C
Receptors, Tumor Necrosis Factor, Member 25
Ligands
Genes
Phosphorylation
Gene Expression
Leukemia, Monocytic, Acute
Activation Analysis
Biological Phenomena
1-Phosphatidylinositol 4-Kinase
Macrophage Activation
Protein C Inhibitor
Tumor Necrosis Factor Receptors
Extracellular Matrix Proteins
Protein Kinase Inhibitors
B-Lymphocytes
Up-Regulation
Western Blotting

Keywords

  • βig-h3
  • Extra cellular matrix
  • Inflammation
  • Macrophage
  • TNFSF

ASJC Scopus subject areas

  • Immunology

Cite this

TL1A induces the expression of TGF-β-inducible gene h3 (βig-h3) through PKC, PI3K, and ERK in THP-1 cells. / Lee, Seung Hee; Kim, Eun Ju; Suk, Kyoungho; Kim, In-San; Lee, Won Ha.

In: Cellular Immunology, Vol. 266, No. 1, 21.09.2010, p. 61-66.

Research output: Contribution to journalArticle

Lee, Seung Hee ; Kim, Eun Ju ; Suk, Kyoungho ; Kim, In-San ; Lee, Won Ha. / TL1A induces the expression of TGF-β-inducible gene h3 (βig-h3) through PKC, PI3K, and ERK in THP-1 cells. In: Cellular Immunology. 2010 ; Vol. 266, No. 1. pp. 61-66.
@article{bc22f1f82efa4d0984460919998c6d1a,
title = "TL1A induces the expression of TGF-β-inducible gene h3 (βig-h3) through PKC, PI3K, and ERK in THP-1 cells",
abstract = "βig-h3, an extracellular matrix protein involved in various biological processes including cellular growth, differentiation, adhesion, migration, and angiogenesis, has been shown to be elevated in various inflammatory processes. Death receptor 3 (DR3), a member of the TNF-receptor superfamily that is expressed on T cells and macrophages, is involved in the regulation of inflammatory processes through interaction with its cognate ligand, TNF-like ligand 1A (TL1A). In order to find out whether the TL1A-induced inflammatory activation of macrophages is associated with the up-regulation of βig-h3 expression, the human acute monocytic leukemia cell line (THP-1) was stimulated with either recombinant human TL1A- or DR3-specific monoclonal antibodies. Stimulation of DR3 up-regulated the intracellular levels as well as the secretion of βig-h3. Utilization of various inhibitors and Western blot analysis revealed that activation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), phosphoinositide kinase-3 (PI3K), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is required for TL1A-induced βig-h3 expression. PKC appears to be the upstream regulator of PI3K since the presence of PKC inhibitor blocked the phosphorylation of AKT without affecting ERK phosphorylation. On the other hand, suppression of either PI3K or ERK activity resulted in the suppression of IκB phosphorylation. These findings indicate that TL1A can regulate the inflammatory processes through modulation of the βig-h3 expression through two separate pathways, one through PKC and PI3K and the other through ERK, which culminates at NF-κB activation.",
keywords = "βig-h3, Extra cellular matrix, Inflammation, Macrophage, TNFSF",
author = "Lee, {Seung Hee} and Kim, {Eun Ju} and Kyoungho Suk and In-San Kim and Lee, {Won Ha}",
year = "2010",
month = "9",
day = "21",
doi = "10.1016/j.cellimm.2010.08.013",
language = "English",
volume = "266",
pages = "61--66",
journal = "Cellular Immunology",
issn = "0008-8749",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - TL1A induces the expression of TGF-β-inducible gene h3 (βig-h3) through PKC, PI3K, and ERK in THP-1 cells

AU - Lee, Seung Hee

AU - Kim, Eun Ju

AU - Suk, Kyoungho

AU - Kim, In-San

AU - Lee, Won Ha

PY - 2010/9/21

Y1 - 2010/9/21

N2 - βig-h3, an extracellular matrix protein involved in various biological processes including cellular growth, differentiation, adhesion, migration, and angiogenesis, has been shown to be elevated in various inflammatory processes. Death receptor 3 (DR3), a member of the TNF-receptor superfamily that is expressed on T cells and macrophages, is involved in the regulation of inflammatory processes through interaction with its cognate ligand, TNF-like ligand 1A (TL1A). In order to find out whether the TL1A-induced inflammatory activation of macrophages is associated with the up-regulation of βig-h3 expression, the human acute monocytic leukemia cell line (THP-1) was stimulated with either recombinant human TL1A- or DR3-specific monoclonal antibodies. Stimulation of DR3 up-regulated the intracellular levels as well as the secretion of βig-h3. Utilization of various inhibitors and Western blot analysis revealed that activation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), phosphoinositide kinase-3 (PI3K), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is required for TL1A-induced βig-h3 expression. PKC appears to be the upstream regulator of PI3K since the presence of PKC inhibitor blocked the phosphorylation of AKT without affecting ERK phosphorylation. On the other hand, suppression of either PI3K or ERK activity resulted in the suppression of IκB phosphorylation. These findings indicate that TL1A can regulate the inflammatory processes through modulation of the βig-h3 expression through two separate pathways, one through PKC and PI3K and the other through ERK, which culminates at NF-κB activation.

AB - βig-h3, an extracellular matrix protein involved in various biological processes including cellular growth, differentiation, adhesion, migration, and angiogenesis, has been shown to be elevated in various inflammatory processes. Death receptor 3 (DR3), a member of the TNF-receptor superfamily that is expressed on T cells and macrophages, is involved in the regulation of inflammatory processes through interaction with its cognate ligand, TNF-like ligand 1A (TL1A). In order to find out whether the TL1A-induced inflammatory activation of macrophages is associated with the up-regulation of βig-h3 expression, the human acute monocytic leukemia cell line (THP-1) was stimulated with either recombinant human TL1A- or DR3-specific monoclonal antibodies. Stimulation of DR3 up-regulated the intracellular levels as well as the secretion of βig-h3. Utilization of various inhibitors and Western blot analysis revealed that activation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), phosphoinositide kinase-3 (PI3K), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is required for TL1A-induced βig-h3 expression. PKC appears to be the upstream regulator of PI3K since the presence of PKC inhibitor blocked the phosphorylation of AKT without affecting ERK phosphorylation. On the other hand, suppression of either PI3K or ERK activity resulted in the suppression of IκB phosphorylation. These findings indicate that TL1A can regulate the inflammatory processes through modulation of the βig-h3 expression through two separate pathways, one through PKC and PI3K and the other through ERK, which culminates at NF-κB activation.

KW - βig-h3

KW - Extra cellular matrix

KW - Inflammation

KW - Macrophage

KW - TNFSF

UR - http://www.scopus.com/inward/record.url?scp=77958488630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77958488630&partnerID=8YFLogxK

U2 - 10.1016/j.cellimm.2010.08.013

DO - 10.1016/j.cellimm.2010.08.013

M3 - Article

VL - 266

SP - 61

EP - 66

JO - Cellular Immunology

JF - Cellular Immunology

SN - 0008-8749

IS - 1

ER -