Abstract
Overexpression of constitutively active (CA)-Gα13 significantly increased the expression of interleukin (IL)-1β and IL-6 mRNAs and proteins in rat cardiac fibroblasts. IL-1β mRNA induction by CA-Gα13 was suppressed by diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, but not by BAPTA-AM, an intracellular Ca2+ chelator. In contrast, IL-6 mRNA induction by CA-Gα13 was suppressed by BAPTA-AM but not by DPI. However, both IL-1β and IL-6 mRNA induction was suppressed by nuclear factor κB (NF-κB) inhibitors. The CA-Gα13-induced NF-κB activation was suppressed by DPI and BAPTA-AM, but not C3 toxin and the Rho-kinase inhibitor Y27632. IL-6 mRNA induction by CA-Gα13 was suppressed by SK&F96365 (1-[β-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride), an inhibitor of receptor-activated nonselective cation channels, and the expression of CA-Gα13 increased basal Ca2+ influx. These results suggest that Gα13 regulates IL-1β mRNA induction through the reactive oxygen species-NF-κB pathway, while it regulates IL-6 mRNA induction through the Ca2+-NF-κB pathway.
| Original language | English |
|---|---|
| Pages (from-to) | 144-150 |
| Number of pages | 7 |
| Journal | Journal of Pharmacological Sciences |
| Volume | 101 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jun 29 2006 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Pharmacology
Cite this
Heterotrimeric G protein Gα13-induced induction of cytokine mRNAs through two distinct pathways in cardiac fibroblasts. / Nagamatsu, Yuichi; Nishida, Motohiro; Onohara, Naoya; Fukutomi, Masashi; Maruyama, Yoshiko; Kobayashi, Hiroyuki; Sato, Yoji; Kurose, Hitoshi.
In: Journal of Pharmacological Sciences, Vol. 101, No. 2, 29.06.2006, p. 144-150.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Heterotrimeric G protein Gα13-induced induction of cytokine mRNAs through two distinct pathways in cardiac fibroblasts
AU - Nagamatsu, Yuichi
AU - Nishida, Motohiro
AU - Onohara, Naoya
AU - Fukutomi, Masashi
AU - Maruyama, Yoshiko
AU - Kobayashi, Hiroyuki
AU - Sato, Yoji
AU - Kurose, Hitoshi
PY - 2006/6/29
Y1 - 2006/6/29
N2 - Overexpression of constitutively active (CA)-Gα13 significantly increased the expression of interleukin (IL)-1β and IL-6 mRNAs and proteins in rat cardiac fibroblasts. IL-1β mRNA induction by CA-Gα13 was suppressed by diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, but not by BAPTA-AM, an intracellular Ca2+ chelator. In contrast, IL-6 mRNA induction by CA-Gα13 was suppressed by BAPTA-AM but not by DPI. However, both IL-1β and IL-6 mRNA induction was suppressed by nuclear factor κB (NF-κB) inhibitors. The CA-Gα13-induced NF-κB activation was suppressed by DPI and BAPTA-AM, but not C3 toxin and the Rho-kinase inhibitor Y27632. IL-6 mRNA induction by CA-Gα13 was suppressed by SK&F96365 (1-[β-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride), an inhibitor of receptor-activated nonselective cation channels, and the expression of CA-Gα13 increased basal Ca2+ influx. These results suggest that Gα13 regulates IL-1β mRNA induction through the reactive oxygen species-NF-κB pathway, while it regulates IL-6 mRNA induction through the Ca2+-NF-κB pathway.
AB - Overexpression of constitutively active (CA)-Gα13 significantly increased the expression of interleukin (IL)-1β and IL-6 mRNAs and proteins in rat cardiac fibroblasts. IL-1β mRNA induction by CA-Gα13 was suppressed by diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, but not by BAPTA-AM, an intracellular Ca2+ chelator. In contrast, IL-6 mRNA induction by CA-Gα13 was suppressed by BAPTA-AM but not by DPI. However, both IL-1β and IL-6 mRNA induction was suppressed by nuclear factor κB (NF-κB) inhibitors. The CA-Gα13-induced NF-κB activation was suppressed by DPI and BAPTA-AM, but not C3 toxin and the Rho-kinase inhibitor Y27632. IL-6 mRNA induction by CA-Gα13 was suppressed by SK&F96365 (1-[β-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride), an inhibitor of receptor-activated nonselective cation channels, and the expression of CA-Gα13 increased basal Ca2+ influx. These results suggest that Gα13 regulates IL-1β mRNA induction through the reactive oxygen species-NF-κB pathway, while it regulates IL-6 mRNA induction through the Ca2+-NF-κB pathway.
UR - http://www.scopus.com/inward/record.url?scp=33745302991&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745302991&partnerID=8YFLogxK
U2 - 10.1254/jphs.FP0051036
DO - 10.1254/jphs.FP0051036
M3 - Article
C2 - 16778360
AN - SCOPUS:33745302991
VL - 101
SP - 144
EP - 150
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8613
IS - 2
ER -