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Abstract
The immune system plays an important role in the pathophysiology of many acute and chronic bone disorders, but the specific inflammatory networks that regulate individual bone disorders remain to be elucidated. Here, we characterized the osteoimmunological underpinnings of osteolytic bone disease in Pstpip2(cmo) mice. These mice carry a homozygous L98P missense mutation in the Pombe Cdc15 homology family phosphatase PSTPIP2 that is responsible for the development of a persistent autoinflammatory disease resembling chronic recurrent multifocal osteomyelitis in humans. We found that improper regulation of IL-1 beta production resulted in secondary induction of inflammatory cytokines, inflammatory cell infiltration in the bone, and unremitting bone inflammation. Aberrant Il1 beta expression precedes the development of osteolytic damage in young Pstpip2(cmo) mice, and genetic deletion of Il1r and Il1 beta, but not Il1 alpha, rescued osteolytic bone disease in mutant mice. Intriguingly, caspase-1 and nucleotide- binding oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 activation in the inflammasome complex were dispensable for Pstpip2(cmo)-mediated bone disease. Thus, our findings establish a critical role for inflammasome- independent production of IL-1 beta in osteolytic bone disease and identify PSTPIP2 as a negative regulator of caspase-1-autonomous IL-1 beta production.
Keywords
CELL-DEATH, T-CELLS, PYOGENIC ARTHRITIS, MULTIFOCAL OSTEOMYELITIS, AUTOINFLAMMATORY DISORDER, PAPA SYNDROME, autoinflammation, interleukin-1, PROTEIN, PYROPTOSOME, ACTIVATION, osteoimmunology, OSTEOIMMUNOLOGY

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Citation

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Chicago
Lukens, John R, Jordan M Gross, Christopher Calabrese, Yoichiro Iwakura, Mohamed Lamkanfi, Peter Vogel, and Thirumala-Devi Kanneganti. 2014. “Critical Role for Inflammasome-independent IL-1β Production in Osteomyelitis.” Proceedings of the National Academy of Sciences of the United States of America 111 (3): 1066–1071.
APA
Lukens, J. R., Gross, J. M., Calabrese, C., Iwakura, Y., Lamkanfi, M., Vogel, P., & Kanneganti, T.-D. (2014). Critical role for inflammasome-independent IL-1β production in osteomyelitis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(3), 1066–1071.
Vancouver
1.
Lukens JR, Gross JM, Calabrese C, Iwakura Y, Lamkanfi M, Vogel P, et al. Critical role for inflammasome-independent IL-1β production in osteomyelitis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2014;111(3):1066–71.
MLA
Lukens, John R, Jordan M Gross, Christopher Calabrese, et al. “Critical Role for Inflammasome-independent IL-1β Production in Osteomyelitis.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111.3 (2014): 1066–1071. Print.
@article{4307382,
  abstract     = {The immune system plays an important role in the pathophysiology of many acute and chronic bone disorders, but the specific inflammatory networks that regulate individual bone disorders remain to be elucidated. Here, we characterized the osteoimmunological underpinnings of osteolytic bone disease in Pstpip2(cmo) mice. These mice carry a homozygous L98P missense mutation in the Pombe Cdc15 homology family phosphatase PSTPIP2 that is responsible for the development of a persistent autoinflammatory disease resembling chronic recurrent multifocal osteomyelitis in humans. We found that improper regulation of IL-1 beta production resulted in secondary induction of inflammatory cytokines, inflammatory cell infiltration in the bone, and unremitting bone inflammation. Aberrant Il1 beta expression precedes the development of osteolytic damage in young Pstpip2(cmo) mice, and genetic deletion of Il1r and Il1 beta, but not Il1 alpha, rescued osteolytic bone disease in mutant mice. Intriguingly, caspase-1 and nucleotide- binding oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 activation in the inflammasome complex were dispensable for Pstpip2(cmo)-mediated bone disease. Thus, our findings establish a critical role for inflammasome- independent production of IL-1 beta in osteolytic bone disease and identify PSTPIP2 as a negative regulator of caspase-1-autonomous IL-1 beta production.},
  author       = {Lukens, John R and Gross, Jordan M and Calabrese, Christopher and Iwakura, Yoichiro and Lamkanfi, Mohamed and Vogel, Peter and Kanneganti, Thirumala-Devi},
  issn         = {0027-8424},
  journal      = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
  keywords     = {CELL-DEATH,T-CELLS,PYOGENIC ARTHRITIS,MULTIFOCAL OSTEOMYELITIS,AUTOINFLAMMATORY DISORDER,PAPA SYNDROME,autoinflammation,interleukin-1,PROTEIN,PYROPTOSOME,ACTIVATION,osteoimmunology,OSTEOIMMUNOLOGY},
  language     = {eng},
  number       = {3},
  pages        = {1066--1071},
  title        = {Critical role for inflammasome-independent IL-1β production in osteomyelitis},
  url          = {http://dx.doi.org/10.1073/pnas.1318688111},
  volume       = {111},
  year         = {2014},
}

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