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Deregulation of the IL-1β axis in chronic recurrent multifocal osteomyelitis.

Scianaro R, Insalaco A, Bracci Laudiero L, De Vito R, Pezzullo M, Teti A, De Benedetti F, Prencipe G - Pediatr Rheumatol Online J (2014)

Bottom Line: The Interleukin (IL)-1β released in the medium of PBMC cultures after treatment with lipopolysaccharides (LPS) alone or LPS and ATP was measured by ELISA.CASP-1 and IL-1β transcript levels were significantly higher also in PBMCs from CRMO patients in remission compared to healthy controls.PBMCs from CRMO patients in active disease stimulated in vitro with LPS showed a significant increase in IL-1β release compared to healthy control cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Rheumatology Unit, Bambino Gesù Children's Hospital, Rome, Italy.

ABSTRACT

Background: This study aims to investigate the inflammasome response in peripheral blood mononuclear cells (PBMCs) and the expression of inflammasome components in bone biopsies from patients with chronic recurrent multifocal osteomyelitis (CRMO).

Methods: The expression of inflammasome components mRNAs was evaluated in PBMCs isolated from 15 CRMO patients and 13 healthy controls by quantitative real-time PCR. The Interleukin (IL)-1β released in the medium of PBMC cultures after treatment with lipopolysaccharides (LPS) alone or LPS and ATP was measured by ELISA. Immunohistochemical staining for Apoptosis-associated Speck-like protein (ASC), caspase-1 (CASP-1), Nod-like receptor protein-3 (NLRP3) and IL-1β expression was performed in bone biopsies from CRMO patients.

Results: mRNA levels of ASC, CASP-1 and IL-1β were significantly higher in freshly isolated PBMCs from CRMO patients in active disease than in healthy controls. CASP-1 and IL-1β transcript levels were significantly higher also in PBMCs from CRMO patients in remission compared to healthy controls. PBMCs from CRMO patients in active disease stimulated in vitro with LPS showed a significant increase in IL-1β release compared to healthy control cells. Immunohistochemistry staining of bone tissue revealed the expression of inflammasome components in CRMO osteoclasts.

Conclusions: Our data suggest that an abnormal regulation of IL-1β axis may be involved in CRMO pathogenesis.

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Related in: MedlinePlus

Expression of inflammasome components and IL-6 in bone biopsies from CRMO patients and from one tissue control. Representative immunohistochemical staining of decalcified human bone biopsy specimens from a tissue control (A-B-C-D-E-F-G) and patients with CRMO (AI-BI-CI-DI-EI-FI-GI). Bone sections were stained with hematoxylin-eosin, a secondary antibody only or with primary antibodies as indicated. Magnification: X63. Arrows: osteoclasts.
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Figure 2: Expression of inflammasome components and IL-6 in bone biopsies from CRMO patients and from one tissue control. Representative immunohistochemical staining of decalcified human bone biopsy specimens from a tissue control (A-B-C-D-E-F-G) and patients with CRMO (AI-BI-CI-DI-EI-FI-GI). Bone sections were stained with hematoxylin-eosin, a secondary antibody only or with primary antibodies as indicated. Magnification: X63. Arrows: osteoclasts.

Mentions: The presence of activated osteoclasts is a typical feature of bone lesions in CRMO. Because of their potential pathogenic role in CRMO, we performed the immunohistochemical staining of bone biopsy specimens from CRMO patients (n = 3), (Figure 2AI-FI) and from one tissue control (Figure 2 A-F) with antibodies to ASC, NLRP3, CASP-1 and IL-1β. In bone tissue from CRMO patients and one control, the expression of the three inflammasome components as well as of IL-1β was detected, demonstrating that also osteoclasts expressed components of the inflammasome machinery.


Deregulation of the IL-1β axis in chronic recurrent multifocal osteomyelitis.

Scianaro R, Insalaco A, Bracci Laudiero L, De Vito R, Pezzullo M, Teti A, De Benedetti F, Prencipe G - Pediatr Rheumatol Online J (2014)

Expression of inflammasome components and IL-6 in bone biopsies from CRMO patients and from one tissue control. Representative immunohistochemical staining of decalcified human bone biopsy specimens from a tissue control (A-B-C-D-E-F-G) and patients with CRMO (AI-BI-CI-DI-EI-FI-GI). Bone sections were stained with hematoxylin-eosin, a secondary antibody only or with primary antibodies as indicated. Magnification: X63. Arrows: osteoclasts.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4109750&req=5

Figure 2: Expression of inflammasome components and IL-6 in bone biopsies from CRMO patients and from one tissue control. Representative immunohistochemical staining of decalcified human bone biopsy specimens from a tissue control (A-B-C-D-E-F-G) and patients with CRMO (AI-BI-CI-DI-EI-FI-GI). Bone sections were stained with hematoxylin-eosin, a secondary antibody only or with primary antibodies as indicated. Magnification: X63. Arrows: osteoclasts.
Mentions: The presence of activated osteoclasts is a typical feature of bone lesions in CRMO. Because of their potential pathogenic role in CRMO, we performed the immunohistochemical staining of bone biopsy specimens from CRMO patients (n = 3), (Figure 2AI-FI) and from one tissue control (Figure 2 A-F) with antibodies to ASC, NLRP3, CASP-1 and IL-1β. In bone tissue from CRMO patients and one control, the expression of the three inflammasome components as well as of IL-1β was detected, demonstrating that also osteoclasts expressed components of the inflammasome machinery.

Bottom Line: The Interleukin (IL)-1β released in the medium of PBMC cultures after treatment with lipopolysaccharides (LPS) alone or LPS and ATP was measured by ELISA.CASP-1 and IL-1β transcript levels were significantly higher also in PBMCs from CRMO patients in remission compared to healthy controls.PBMCs from CRMO patients in active disease stimulated in vitro with LPS showed a significant increase in IL-1β release compared to healthy control cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Rheumatology Unit, Bambino Gesù Children's Hospital, Rome, Italy.

ABSTRACT

Background: This study aims to investigate the inflammasome response in peripheral blood mononuclear cells (PBMCs) and the expression of inflammasome components in bone biopsies from patients with chronic recurrent multifocal osteomyelitis (CRMO).

Methods: The expression of inflammasome components mRNAs was evaluated in PBMCs isolated from 15 CRMO patients and 13 healthy controls by quantitative real-time PCR. The Interleukin (IL)-1β released in the medium of PBMC cultures after treatment with lipopolysaccharides (LPS) alone or LPS and ATP was measured by ELISA. Immunohistochemical staining for Apoptosis-associated Speck-like protein (ASC), caspase-1 (CASP-1), Nod-like receptor protein-3 (NLRP3) and IL-1β expression was performed in bone biopsies from CRMO patients.

Results: mRNA levels of ASC, CASP-1 and IL-1β were significantly higher in freshly isolated PBMCs from CRMO patients in active disease than in healthy controls. CASP-1 and IL-1β transcript levels were significantly higher also in PBMCs from CRMO patients in remission compared to healthy controls. PBMCs from CRMO patients in active disease stimulated in vitro with LPS showed a significant increase in IL-1β release compared to healthy control cells. Immunohistochemistry staining of bone tissue revealed the expression of inflammasome components in CRMO osteoclasts.

Conclusions: Our data suggest that an abnormal regulation of IL-1β axis may be involved in CRMO pathogenesis.

Show MeSH
Related in: MedlinePlus