Abstract
Since the endocrine and immune systems share portions of some intracellular signaling pathways, endocrine-disrupting chemicals (EDCs) are considered potential agents for influencing inflammatory responses. Here, we investigated the effect of EDCs on lipopolysaccharide (LPS)-induced NO production and NF-κB activation in the RAW264.7 mouse macrophage cell line. Five phenol-containing EDCs were investigated, namely bisphenol A (BPA), the alkyl phenols p-n-nonylphenol (NP) and p-n-octylphenol (OP), and the chlorinated phenols 2,4-dichlorophenol (DCP) and pentachlorophenol (PCP). Our results revealed that these chemicals dose-dependently suppressed LPS-induced NO production, as reflected by decreased NOx content. The suppressive effects of BPA, NP and OP, but not PCP or DCP, were blocked by the estrogen receptor (ER) inhibitor, ICI182780. ELISA-based quantification of the DNA-binding activity of free p65 NF-κB showed that LPS-induced NF-κB activation was significantly diminished by EDC treatment. Furthermore, immunocytochemical analysis of 8-nitroguanosine, a unique index of NO-mediated signaling, showed that 8-nitroguanosine formation increased in LPS-stimulated cells, but this increase was inhibited by the tested EDCs. These results demonstrate that EDCs suppress NO production and NF-κB activation in LPS-stimulated macrophages through ER-dependent (BPA, NP, OP) and -independent (PCP, DCP) pathways. The EDCs further inhibited 8-nitroguanosine formation, suggesting that they interfere with NO-mediated signaling. Thus, EDCs might play important roles in the inflammatory response and host defense system against foreign pathogens.
| Original language | English |
|---|---|
| Pages (from-to) | 223-228 |
| Number of pages | 6 |
| Journal | Nitric Oxide - Biology and Chemistry |
| Volume | 18 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - May 2008 |
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Keywords
- 8-Nitroguanosine
- Endocrine-disrupting chemicals
- Estrogen receptor
- iNOS
- NF-κB
- Nitric oxide
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
Cite this
Suppression of NO production and 8-nitroguanosine formation by phenol-containing endocrine-disrupting chemicals in LPS-stimulated macrophages : Involvement of estrogen receptor-dependent or -independent pathways. / Yoshitake, Jun; Kato, Katsuaki; Yoshioka, Daisuke; Sueishi, Yoshimi; Sawa, Tomohiro; Akaike, Takaaki; Yoshimura, Tetsuhiko.
In: Nitric Oxide - Biology and Chemistry, Vol. 18, No. 3, 05.2008, p. 223-228.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Suppression of NO production and 8-nitroguanosine formation by phenol-containing endocrine-disrupting chemicals in LPS-stimulated macrophages
T2 - Involvement of estrogen receptor-dependent or -independent pathways
AU - Yoshitake, Jun
AU - Kato, Katsuaki
AU - Yoshioka, Daisuke
AU - Sueishi, Yoshimi
AU - Sawa, Tomohiro
AU - Akaike, Takaaki
AU - Yoshimura, Tetsuhiko
PY - 2008/5
Y1 - 2008/5
N2 - Since the endocrine and immune systems share portions of some intracellular signaling pathways, endocrine-disrupting chemicals (EDCs) are considered potential agents for influencing inflammatory responses. Here, we investigated the effect of EDCs on lipopolysaccharide (LPS)-induced NO production and NF-κB activation in the RAW264.7 mouse macrophage cell line. Five phenol-containing EDCs were investigated, namely bisphenol A (BPA), the alkyl phenols p-n-nonylphenol (NP) and p-n-octylphenol (OP), and the chlorinated phenols 2,4-dichlorophenol (DCP) and pentachlorophenol (PCP). Our results revealed that these chemicals dose-dependently suppressed LPS-induced NO production, as reflected by decreased NOx content. The suppressive effects of BPA, NP and OP, but not PCP or DCP, were blocked by the estrogen receptor (ER) inhibitor, ICI182780. ELISA-based quantification of the DNA-binding activity of free p65 NF-κB showed that LPS-induced NF-κB activation was significantly diminished by EDC treatment. Furthermore, immunocytochemical analysis of 8-nitroguanosine, a unique index of NO-mediated signaling, showed that 8-nitroguanosine formation increased in LPS-stimulated cells, but this increase was inhibited by the tested EDCs. These results demonstrate that EDCs suppress NO production and NF-κB activation in LPS-stimulated macrophages through ER-dependent (BPA, NP, OP) and -independent (PCP, DCP) pathways. The EDCs further inhibited 8-nitroguanosine formation, suggesting that they interfere with NO-mediated signaling. Thus, EDCs might play important roles in the inflammatory response and host defense system against foreign pathogens.
AB - Since the endocrine and immune systems share portions of some intracellular signaling pathways, endocrine-disrupting chemicals (EDCs) are considered potential agents for influencing inflammatory responses. Here, we investigated the effect of EDCs on lipopolysaccharide (LPS)-induced NO production and NF-κB activation in the RAW264.7 mouse macrophage cell line. Five phenol-containing EDCs were investigated, namely bisphenol A (BPA), the alkyl phenols p-n-nonylphenol (NP) and p-n-octylphenol (OP), and the chlorinated phenols 2,4-dichlorophenol (DCP) and pentachlorophenol (PCP). Our results revealed that these chemicals dose-dependently suppressed LPS-induced NO production, as reflected by decreased NOx content. The suppressive effects of BPA, NP and OP, but not PCP or DCP, were blocked by the estrogen receptor (ER) inhibitor, ICI182780. ELISA-based quantification of the DNA-binding activity of free p65 NF-κB showed that LPS-induced NF-κB activation was significantly diminished by EDC treatment. Furthermore, immunocytochemical analysis of 8-nitroguanosine, a unique index of NO-mediated signaling, showed that 8-nitroguanosine formation increased in LPS-stimulated cells, but this increase was inhibited by the tested EDCs. These results demonstrate that EDCs suppress NO production and NF-κB activation in LPS-stimulated macrophages through ER-dependent (BPA, NP, OP) and -independent (PCP, DCP) pathways. The EDCs further inhibited 8-nitroguanosine formation, suggesting that they interfere with NO-mediated signaling. Thus, EDCs might play important roles in the inflammatory response and host defense system against foreign pathogens.
KW - 8-Nitroguanosine
KW - Endocrine-disrupting chemicals
KW - Estrogen receptor
KW - iNOS
KW - NF-κB
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=41149107750&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41149107750&partnerID=8YFLogxK
U2 - 10.1016/j.niox.2008.01.003
DO - 10.1016/j.niox.2008.01.003
M3 - Article
C2 - 18252206
AN - SCOPUS:41149107750
VL - 18
SP - 223
EP - 228
JO - Nitric Oxide - Biology and Chemistry
JF - Nitric Oxide - Biology and Chemistry
SN - 1089-8603
IS - 3
ER -