Glibenclamide inhibits NLRP3 inflammasome-mediated IL-1β secretion in human trophoblasts
Infection-associated pregnancy complications cause premature delivery. Caspase-1 is involved in the maturation of interleukin (IL)-1β, which is activated by the NLRP3 inflammasome. To characterize the significance of the NLRP3 inflammasome pathway in the placenta, the effects of activators and inhi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-10-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861317301640 |
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| author | Kazuhiro Tamura Gen Ishikawa Mikihiro Yoshie Wakana Ohneda Akihito Nakai Toshiyuki Takeshita Eiichi Tachikawa |
| author_facet | Kazuhiro Tamura Gen Ishikawa Mikihiro Yoshie Wakana Ohneda Akihito Nakai Toshiyuki Takeshita Eiichi Tachikawa |
| author_sort | Kazuhiro Tamura |
| collection | DOAJ |
| description | Infection-associated pregnancy complications cause premature delivery. Caspase-1 is involved in the maturation of interleukin (IL)-1β, which is activated by the NLRP3 inflammasome. To characterize the significance of the NLRP3 inflammasome pathway in the placenta, the effects of activators and inhibitors on NLRP3-related molecules were examined using isolated primary trophoblasts. Caspase-1 and IL-1β mRNA expression was markedly increased in response to lipopolysaccharide (LPS), a toll-like receptor (TLR)4 ligand. Treatment with the potassium ionophore nigericin significantly increased the level of activated caspase-1. Treatment with either LPS or nigericin stimulated IL-1β secretion, whereas pretreatment with the ATP-sensitive K+ channel inhibitor glibenclamide, the Rho-associated coiled-coil kinase inhibitor Y-27632, or a caspase-1 inhibitor significantly decreased nigericin-induced IL-1β secretion. In addition, dibutyryl-cAMP, which induces trophoblast differentiation, decreased expression of NLRP3, caspase-1, and IL-1β. These findings suggest that trophoblasts can secrete IL-1β through the NLRP3/caspase-1 pathway, which is suppressed by glibenclamide, and that the TLR4-mediated NLRP3 inflammasome pathway is more likely to be stimulated in undifferentiated than differentiated trophoblasts. Our data support the hypothesis that inhibition of the NLRP3 inflammasome can suppress placental inflammation-associated disorders. Keywords: Inflammasome, TLR4, NLRP3, Caspase-1, Trophoblast |
| first_indexed | 2024-04-14T02:24:44Z |
| format | Article |
| id | doaj.art-a87c5b7c6c5e43159dadeca50bc8f9cb |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-14T02:24:44Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-a87c5b7c6c5e43159dadeca50bc8f9cb2022-12-22T02:17:55ZengElsevierJournal of Pharmacological Sciences1347-86132017-10-0113528995Glibenclamide inhibits NLRP3 inflammasome-mediated IL-1β secretion in human trophoblastsKazuhiro Tamura0Gen Ishikawa1Mikihiro Yoshie2Wakana Ohneda3Akihito Nakai4Toshiyuki Takeshita5Eiichi Tachikawa6Department of Endocrine & Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan; Corresponding author. Fax: +81 42 676 4536.Department of Obstetrics and Gynecology, Nippon Medical School, 1-7-1, Nagayama, Tokyo 160-0023, JapanDepartment of Endocrine & Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDepartment of Endocrine & Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDepartment of Obstetrics and Gynecology, Nippon Medical School, 1-7-1, Nagayama, Tokyo 160-0023, JapanDepartment of Obstetrics and Gynecology, Nippon Medical School, 1-1-5, Bunkyo, Tokyo 113-8603, JapanDepartment of Endocrine & Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanInfection-associated pregnancy complications cause premature delivery. Caspase-1 is involved in the maturation of interleukin (IL)-1β, which is activated by the NLRP3 inflammasome. To characterize the significance of the NLRP3 inflammasome pathway in the placenta, the effects of activators and inhibitors on NLRP3-related molecules were examined using isolated primary trophoblasts. Caspase-1 and IL-1β mRNA expression was markedly increased in response to lipopolysaccharide (LPS), a toll-like receptor (TLR)4 ligand. Treatment with the potassium ionophore nigericin significantly increased the level of activated caspase-1. Treatment with either LPS or nigericin stimulated IL-1β secretion, whereas pretreatment with the ATP-sensitive K+ channel inhibitor glibenclamide, the Rho-associated coiled-coil kinase inhibitor Y-27632, or a caspase-1 inhibitor significantly decreased nigericin-induced IL-1β secretion. In addition, dibutyryl-cAMP, which induces trophoblast differentiation, decreased expression of NLRP3, caspase-1, and IL-1β. These findings suggest that trophoblasts can secrete IL-1β through the NLRP3/caspase-1 pathway, which is suppressed by glibenclamide, and that the TLR4-mediated NLRP3 inflammasome pathway is more likely to be stimulated in undifferentiated than differentiated trophoblasts. Our data support the hypothesis that inhibition of the NLRP3 inflammasome can suppress placental inflammation-associated disorders. Keywords: Inflammasome, TLR4, NLRP3, Caspase-1, Trophoblasthttp://www.sciencedirect.com/science/article/pii/S1347861317301640 |
| spellingShingle | Kazuhiro Tamura Gen Ishikawa Mikihiro Yoshie Wakana Ohneda Akihito Nakai Toshiyuki Takeshita Eiichi Tachikawa Glibenclamide inhibits NLRP3 inflammasome-mediated IL-1β secretion in human trophoblasts Journal of Pharmacological Sciences |
| title | Glibenclamide inhibits NLRP3 inflammasome-mediated IL-1β secretion in human trophoblasts |
| title_full | Glibenclamide inhibits NLRP3 inflammasome-mediated IL-1β secretion in human trophoblasts |
| title_fullStr | Glibenclamide inhibits NLRP3 inflammasome-mediated IL-1β secretion in human trophoblasts |
| title_full_unstemmed | Glibenclamide inhibits NLRP3 inflammasome-mediated IL-1β secretion in human trophoblasts |
| title_short | Glibenclamide inhibits NLRP3 inflammasome-mediated IL-1β secretion in human trophoblasts |
| title_sort | glibenclamide inhibits nlrp3 inflammasome mediated il 1i² secretion in human trophoblasts |
| url | http://www.sciencedirect.com/science/article/pii/S1347861317301640 |
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