title: IL-18BP is decreased in osteoporotic women: Prevents Inflammasome mediated IL-18 activation and reduces Th17 differentiation.
abstract: IL-18BP is a natural antagonist of pro-inflammatory IL-18 cytokine linked to autoimmune disorders like rheumatoid arthritis. However, its role in post menopausal osteoporosis is still unknown. In this study, we investigated the role of IL-18BP on murine osteoblasts, its effect on osteoblasts-CD4+ T cells and osteoblasts-CD11b+ macrophage co-culture. mIL-18BPd enhances osteoblast differentiation and inhibits the activation of NLRP3 inflammasome and caspase-1 which process IL-18 to its active form. Using estrogen deficient mice, we also determined the effect of mIL-18BP on various immune and skeletal parameters. Ovariectomized mice treated with mIL-18BPd exhibited decrease in Th17/Treg ratio and pro-inflammatory cytokines. mIL-18BPd treatment restored trabecular microarchitecture, preserved cortical bone parameters likely attributed to an increased number of bone lining cells and reduced osteoclastogenesis. Importantly, these results were corroborated in female osteoporotic subjects where decreased serum IL-18BP levels and enhanced serum IL-18 levels were observed. Our study forms a strong basis for using humanized IL-18BP towards the treatment of postmenopausal osteoporosis.
authors.affiliation: Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India.
authors.forename: Mohd Nizam
authors.initials: MN
authors.lastname: Mansoori
authors.affiliation: Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Shukla
authors.affiliation: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Kakaji
authors.affiliation: Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India.
authors.forename: Abdul M
authors.initials: AM
authors.lastname: Tyagi
authors.affiliation: Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India.
authors.forename: Kamini
authors.initials: K
authors.lastname: Srivastava
authors.affiliation: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Shukla
authors.affiliation: Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Dixit
authors.affiliation: Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Kureel
authors.affiliation: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Sushil
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020382:Interleukin-18 / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D015663:Osteoporosis, Postmenopausal / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D014157:Transcription Factors; C118370:interleukin-18 binding protein