Effects of Zoledronate on Local and Systemic Production of IL-1β, IL-18, and TNF-α in Mice and Augmentation by Lipopolysaccharide
-
- Funayama Hiromi
- Department of Pediatric Dentistry, Tsurumi University School of Dental Medicine
-
- Tashima Itaru
- Department of Pediatric Dentistry, Tsurumi University School of Dental Medicine
-
- Okada Satoru
- Division of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Tohoku University
-
- Ogawa Takuya
- Division of Cell Biology, Department of Pharmaceutical Sciences, School of Pharmacy, International University of Health and Welfare
-
- Yagi Hideki
- Division of Immunobiology, Department of Pharmaceutical Sciences, School of Pharmacy, International University of Health and Welfare
-
- Tada Hiroyuki
- Division of Oral Molecular Regulation, Graduate School of Dentistry, Tohoku University
-
- Wakita Ryo
- Section of Anesthesiology and Clinical Physiology, Department of Oral Restitution, Division of Oral Health Sciences, Graduate School, Tokyo Medical and Dental University
-
- Asada Yoshinobu
- Department of Pediatric Dentistry, Tsurumi University School of Dental Medicine
-
- Endo Yasuo
- Division of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Tohoku University
Search this article
Abstract
<p>Bisphosphonates (BPs) containing nitrogen (N-BPs) exhibit far stronger anti-bone-resorptive effects than non-N-BPs. However, repeated administration of N-BPs causes osteonecrosis selectively in jawbones. As BPs accumulate in large amounts within inflamed bones, any N-BP released from the pool accumulated within jawbones might directly act on cells in the surrounding soft-tissues and induce inflammation or necrosis. Here, we examined the local and systemic effects of zoledronate (the most potent N-BP with the highest incidence of jawbone-necrosis) on inflammatory cytokines in mice. Locally within ear-pinnas: (i) zoledronate induced long-lasting accumulation of interleuikin-1β (IL-1β) and IL-18, but not tumor necrosis factor-α (TNF-α), (ii) zoledronate and lipopolysaccharide (LPS, a cell-wall component of Gram-negative bacteria) mutually augmented the productions of IL-1β, IL-18, and TNF-α, and (iii) oxidronate (a toxic non-N-BP) by itself produced not only IL-1β and IL-18, but also TNF-α. In systemic experiments using intraperitoneal injection of zoledronate and/or LPS, (i) zoledronate by itself increased none of the above cytokines in serum, and (ii) in mice pretreated (3 d before) with zoledronate, the LPS-induced increases in serum IL-1β and IL-18 were greatly augmented with a delayed slight TNF-α augmentation. These results, together with previous ones, suggest that (a) pro-IL-1β and pro-IL-18 accumulate within cells in soft-tissues exposed to N-BPs, and infection may augment not only their production, but also the release of their mature forms, (b) IL-1β and IL-18 (possibly together with TNF-α) may play important roles in N-BP-induced inflammation and/or necrosis, and (c) mechanisms underlying the cytotoxic effects of BPs may differ between N-BPs and non-N-BPs.</p>
Journal
-
- Biological and Pharmaceutical Bulletin
-
Biological and Pharmaceutical Bulletin 42 (6), 929-936, 2019-06-01
The Pharmaceutical Society of Japan
- Tweet
Keywords
Details 詳細情報について
-
- CRID
- 1390564238095681920
-
- NII Article ID
- 130007657675
-
- NII Book ID
- AA10885497
-
- ISSN
- 13475215
- 09186158
-
- NDL BIB ID
- 029698385
-
- PubMed
- 31155589
-
- Text Lang
- en
-
- Data Source
-
- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
-
- Abstract License Flag
- Disallowed