The Physiopathological Role of IL-33: New Highlights in Bone Biology and a Proposed Role in Periodontal Disease

Luz, Felipe Andrés Cordero da; Oliveira, Ana Paula de Lima; Borges, Daniella Cristina; Brígido, Paula Cristina; Silva, Marcelo José Barbosa

doi:10.1155/2014/342410

Cited by 22 publications

(17 citation statements)

References 47 publications

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“…We found that plasma levels of sST2, the decoy receptor of IL-33, were independently associated with both the presence of carotid plaque and compromised cortical vBMD/microstructure, which supported the hypotheses. Our results further extended the previously isolated knowledge about the role of this axis on each condition67, by exploring the the overall association among IL-33/ST2 axis, atherosclerosis and osteoporosis.…”

Section: Discussionsupporting

confidence: 73%

Carotid plaque and bone density and microarchitecture in psoriatic arthritis: the correlation with soluble ST2

Shen

Shang

Wong

et al. 2016

Sci Rep

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Psoriatic arthritis (PsA) patients have increased risk of both atherosclerosis and osteoporosis. Previous studies revealed that IL-33/ST2 axis may be related to both conditions; however, these associations were never evaluated in a single patients’ group. Here we explored the association among plasma levels of IL-33 and its decoy receptor soluble ST2 (sST2), carotid plaque determined by ultrasound, and volumetric bone mineral density (vBMD)/microstructure of distal radius measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 80 PsA patients (55% male; 53.0 ± 10.1 years). Plasma sST2 levels were significantly higher in 33 (41%) patients with carotid plaques (11.2 ± 4.5 vs 7.7 ± 3.7 ng/ml, P < 0.001). In multivariate analysis, sST2 was an independent explanatory variable associated with carotid plaques (OR = 1.296, 95% CI: [1.091,1.540]; P = 0.003). After adjustment for the osteoporotic risk factors, sST2 was significantly associated with higher cortical porosity (β = 0.184, [0.042,0.325]; P = 0.012) and cortical pore volume (2.247, [0.434,4.060]; P = 0.016); and had a trend to be associated with lower cortical vBMD (−2.918, [−6.111,0.275]; P = 0.073). IL-33 was not associated with carotid plaque or vBMD/microstructure. In conclusion, plasma sST2 levels were independently correlated with both carotid plaque and compromised cortical vBMD/microstructure in PsA patients. IL-33/ST2 axis may be a link between accelerated atherosclerosis and osteoporosis in PsA.

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Section: Discussionsupporting

confidence: 73%

Carotid plaque and bone density and microarchitecture in psoriatic arthritis: the correlation with soluble ST2

Shen

Shang

Wong

et al. 2016

Sci Rep

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“…However antibodies directed against these 3 cytokines did not exhibit a convincing therapeutic effect in periodontitis, thereby strongly suggesting that others mediators could be involved in the pathogenesis of this disease [8]. Recently, it has been suggested that among inflammatory mediators involved in chronic periodontitis (CP), a member of the IL-1 family, IL-33, could play a role in the initiation and the progression of CP [9]. …”

Section: Introductionmentioning

confidence: 99%

Interleukin-33 and RANK-L Interplay in the Alveolar Bone Loss Associated to Periodontitis

Lapérine

Cloître

Caillon³

et al. 2016

PLoS ONE

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IntroductionChronic Periodontitis (CP) is an inflammatory disease of bacterial origin that results in alveolar bone destruction. Porphyromonas gingivalis (Pg), one of the main periopathogens, initiates an inflammatory cascade by host immune cells thereby increasing recruitment and activity of osteoclasts, the bone resorbing cells, through enhanced production of the crucial osteoclastogenic factor, RANK-L. Antibodies directed against some cytokines (IL-1β, IL-6 and TNF-α) failed to exhibit convincing therapeutic effect in CP. It has been suggested that IL-33, could be of interest in CP.Objectivethe present study aims to analyze whether and how IL-33 and RANK-L and/or their interplay are involved in the bone destruction associated to CP.Material and MethodsmRNAs and protein expressions of IL-33 and RANK-L were analyzed in healthy and CP human gingival samples by immunohistochemistry (IHC) and RT-qPCR. Murine experimental periodontitis (EP) was induced using Pg infected ligature and Pg free ligature around the first maxillary molar. Alveolar bone loss was recorded by μCT. Mouse gingival explants were stimulated for 24 hours with IL-33 and RANK-L mRNA expression investigated by RT-qPCR. Human oral epithelial cells were infected by Pg for 6, 12; 24 hours and IL-33 and RANK-L mRNA expressions were analyzed by RT-qPCR.ResultsIL-33 is overexpressed in gingival epithelial cells in human affected by CP as in the murine EP. In human as in murine gingival cells, RANK-L was independently induced by Pg and IL-33. We also showed that the Pg-dependent RANK-L expression in gingival epithelial cells occured earlier than that of IL-33.ConclusionOur results evidence that IL-33 overexpression in gingival epithelial cells is associated with CP and may trigger RANK-L expression in addition to a direct effect of Pg. Finally, IL-33 may act as an extracellular alarmin (danger signal) showing proinflammatory properties in CP perpetuating bone resorption induced by Pg infection.

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“…The results showed that IL-33 inhibited RANKL-and TNF-α-induced osteoclastogenesis from bone marrow macrophages. Whereas a number of studies have examined the disease-associated functions of IL-33, including in asthma, allergy, anaphylaxis, cardiovascular disease, and the nervous system [11], few studies have focused on the role of IL-33 in bone metabolism [23]. In the present study, we cultured osteoclast precursors in the presence of M-CSF and RANKL.…”

Section: Discussionmentioning

confidence: 97%

IL-33 Inhibits TNF-α-Induced Osteoclastogenesis and Bone Resorption

Ohori

Kitaura

Ogawa

et al. 2020

IJMS

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Interleukin (IL)-33 is a member of the IL-1 family, which acts as an alarmin. Several studies suggested that IL-33 inhibited osteoclastogenesis and bone resorption. Tumor necrosis factor-α (TNF-α) is considered a direct inducer of osteoclastogenesis. However, there has been no report regarding the effect of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. The objective of this study is to investigate the role of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. In an in vitro analysis of osteoclastogenesis, osteoclast precursors, which were derived from bone marrow cells, were treated with or without IL-33 in the presence of TNF-α. Tartrate-resistant acid phosphatase (TRAP) staining solution was used to assess osteoclast formation. In an in vivo analysis of mouse calvariae, TNF-α with or without IL-33 was subcutaneously administrated into the supracalvarial region of mice daily for 5 days. Histological sections were stained for TRAP, and osteoclast numbers were determined. Using micro-CT reconstruction images, the ratio of bone destruction area on the calvariae was evaluated. The number of TRAP-positive cells induced by TNF-α was significantly decreased with IL-33 in vitro and in vivo. Bone resorption was also reduced. IL-33 inhibited IκB phosphorylation and NF-κB nuclear translocation. These results suggest that IL-33 inhibited TNF-α-induced osteoclastogenesis and bone resorption.

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The Physiopathological Role of IL-33: New Highlights in Bone Biology and a Proposed Role in Periodontal Disease

Cited by 22 publications

References 47 publications

Carotid plaque and bone density and microarchitecture in psoriatic arthritis: the correlation with soluble ST2

Carotid plaque and bone density and microarchitecture in psoriatic arthritis: the correlation with soluble ST2

Interleukin-33 and RANK-L Interplay in the Alveolar Bone Loss Associated to Periodontitis

IL-33 Inhibits TNF-α-Induced Osteoclastogenesis and Bone Resorption

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