PMID- 25795135 OWN - NLM STAT- MEDLINE DCOM- 20150728 LR - 20171116 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 460 IP - 2 DP - 2015 May 1 TI - IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression. PG - 320-6 LID - S0006-291X(15)00468-4 [pii] LID - 10.1016/j.bbrc.2015.03.033 [doi] AB - Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-kappaB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Kiyomiya, Hiroyasu AU - Kiyomiya H AD - Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan; Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. FAU - Ariyoshi, Wataru AU - Ariyoshi W AD - Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. FAU - Okinaga, Toshinori AU - Okinaga T AD - Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. FAU - Kaneuji, Takeshi AU - Kaneuji T AD - Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. FAU - Mitsugi, Sho AU - Mitsugi S AD - Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. FAU - Sakurai, Takuma AU - Sakurai T AD - Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan; Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. FAU - Habu, Manabu AU - Habu M AD - Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. FAU - Yoshioka, Izumi AU - Yoshioka I AD - Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. FAU - Tominaga, Kazuhiro AU - Tominaga K AD - Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. FAU - Nishihara, Tatsuji AU - Nishihara T AD - Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. Electronic address: tatsujin@kyu-dent.ac.jp. LA - eng PT - Journal Article DEP - 20150318 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (DNA Primers) RN - 0 (Il33 protein, mouse) RN - 0 (Interferon Regulatory Factors) RN - 0 (Interleukin-33) RN - 0 (Interleukins) RN - 0 (NFATC Transcription Factors) RN - 0 (Nfatc1 protein, mouse) RN - 0 (Prdm1 protein, mouse) RN - 0 (RANK Ligand) RN - 0 (Tnfsf11 protein, mouse) RN - 0 (Transcription Factors) RN - 0 (interferon regulatory factor-8) RN - EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1) SB - IM MH - Animals MH - Base Sequence MH - Cell Line MH - Cells, Cultured MH - DNA Primers MH - Female MH - Interferon Regulatory Factors/genetics/*metabolism MH - Interleukin-33 MH - Interleukins/*physiology MH - Male MH - Mice MH - NFATC Transcription Factors/genetics/metabolism MH - Osteoclasts/*cytology MH - Positive Regulatory Domain I-Binding Factor 1 MH - RANK Ligand/*antagonists & inhibitors/physiology MH - Real-Time Polymerase Chain Reaction MH - Signal Transduction MH - Transcription Factors/genetics/*metabolism OTO - NOTNLM OT - Blimp-1 OT - IL-33 OT - IRF-8 OT - Osteoclastogenesis EDAT- 2015/03/22 06:00 MHDA- 2015/07/29 06:00 CRDT- 2015/03/22 06:00 PHST- 2015/02/23 00:00 [received] PHST- 2015/03/07 00:00 [accepted] PHST- 2015/03/22 06:00 [entrez] PHST- 2015/03/22 06:00 [pubmed] PHST- 2015/07/29 06:00 [medline] AID - S0006-291X(15)00468-4 [pii] AID - 10.1016/j.bbrc.2015.03.033 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2015 May 1;460(2):320-6. doi: 10.1016/j.bbrc.2015.03.033. Epub 2015 Mar 18.