Critical role of LTB4/BLT1 in IL-23-induced synovial inflammation and osteoclastogenesis via NF-κB

Laura Bouchareychas, Eva M. Grössinger, Mincheol Kang, Hong Qiu, Iannis Adamopoulos

Research output: Contribution to journalArticle

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Abstract

IL-23 activates the synthesis and production of leukotriene B4 (LTB4) in myeloid cells, which modulate inflammatory arthritis. In this study we investigated the role of LTB4 and its receptor LTB4R1 (BLT1) in synovial inflammation and osteoclast differentiation. Specifically, we used IL-23 in vivo gene transfer to induce arthritis in mice and showed that elevated serum LTB4 and synovial expression of 5-lipoxygenase correlated with increased disease severity by histological evaluation and paw swelling compared with GFP gene transfer controls. To further investigate the effect of the LTB4 pathway in bone loss, we performed osteoclast differentiation assays by stimulating with M-CSF and receptor activator of NF-κB ligand bone marrow cells derived from BLT1+/+ and/or BLT1-/- mice and used quantitative PCR for gene expression analysis in terminally differentiated osteoclasts. Deficiency in BLT1 resulted in the upregulation of osteoclast-related genes and an increase in the formation of giant, multinucleated TRAP+ cells capable of F-actin ring formation. Additionally, BLT1 deficiency showed an increase of phosphorylated NF-κB and phosphorylated IκB levels in osteoclasts. We also performed real-time calcium imaging to study the effect of BLT1 deficiency in receptor activator of NF-κ-B ligand-induced activation of intracellular calcium flux in vitro. Our data show that LTB4 and its receptor BLT1 exacerbate synovial inflammation in vivo and bone resorption in vitro, suggesting that LTB4 and BLT1 could be effectively targeted for the treatment of musculoskeletal diseases.

Original languageEnglish (US)
Pages (from-to)452-460
Number of pages9
JournalJournal of Immunology
Volume198
Issue number1
DOIs
StatePublished - Jan 1 2017

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Interleukin-23
Leukotriene B4
Osteoclasts
Osteogenesis
Inflammation
Leukotriene B4 Receptors
Arthritis
Macrophage Colony-Stimulating Factor Receptors
Musculoskeletal Diseases
Genes
Ligands
Calcium
Arachidonate 5-Lipoxygenase
Myeloid Cells
Giant Cells
Bone Resorption
Bone Marrow Cells
Actins
Up-Regulation
Gene Expression

ASJC Scopus subject areas

  • Immunology

Cite this

Critical role of LTB4/BLT1 in IL-23-induced synovial inflammation and osteoclastogenesis via NF-κB. / Bouchareychas, Laura; Grössinger, Eva M.; Kang, Mincheol; Qiu, Hong; Adamopoulos, Iannis.

In: Journal of Immunology, Vol. 198, No. 1, 01.01.2017, p. 452-460.

Research output: Contribution to journalArticle

Bouchareychas, Laura ; Grössinger, Eva M. ; Kang, Mincheol ; Qiu, Hong ; Adamopoulos, Iannis. / Critical role of LTB4/BLT1 in IL-23-induced synovial inflammation and osteoclastogenesis via NF-κB. In: Journal of Immunology. 2017 ; Vol. 198, No. 1. pp. 452-460.
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