Basic calcium phosphate crystals induce monocyte/macrophage IL-1β secretion through the NLRP3 inflammasome in vitro.
Basic calcium phosphate (BCP) crystals are associated with severe osteoarthritis and acute periarticular inflammation. Three main forms of BCP crystals have been identified from pathological tissues: octacalcium phosphate, carbonate-substituted apatite, and hydroxyapatite. We investigated the proinflammatory effects of these BCP crystals in vitro with special regard to the involvement of the NLRP3-inflammasome in THP-1 cells, primary human monocytes and macrophages, and mouse bone marrow-derived macrophages (BMDM). THP-1 cells stimulated with BCP crystals produced IL-1β in a dose-dependent manner. Similarly, primary human cells and BMDM from wild-type mice also produced high concentrations of IL-1β after crystal stimulation. THP-1 cells transfected with short hairpin RNA against the components of the NLRP3 inflammasome and mouse BMDM from mice deficient for NLRP3, apoptosis-associated speck-like protein, or caspase-1 did not produce IL-1β after BCP crystal stimulation. BCP crystals induced macrophage apoptosis/necrosis as demonstrated by MTT and flow cytometric analysis. Collectively, these results demonstrate that BCP crystals induce IL-1β secretion through activating the NLRP3 inflammasome. Furthermore, we speculate that IL-1 blockade could be a novel strategy to inhibit BCP-induced inflammation in human disease.
Department of Rheumatology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
Borbála
B
Pazár
Hang-Korng
HK
Ea
Sharmal
S
Narayan
Laeticia
L
Kolly
Nathalie
N
Bagnoud
Véronique
V
Chobaz
Thierry
T
Roger
Frédéric
F
Lioté
Alexander
A
So
Nathalie
N
Busso
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002130:Calcium Phosphates / Q000494:pharmacology*; D002131:Calcium Pyrophosphate / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology*; D020170:Caspase 1 / Q000172:deficiency / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003460:Crystallization; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism / Q000502:physiology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D014527:Uric Acid / Q000494:pharmacology
D002130:Calcium Phosphates; D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse; D014527:Uric Acid; C020243:calcium phosphate; D020170:Caspase 1; D002131:Calcium Pyrophosphate