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 language | English |
|---|---|
| Pages (from-to) | 61-66 |
| Number of pages | 6 |
| Journal | Cellular Immunology |
| Volume | 266 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2010 Sep 21 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
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 -