Elevated levels of Interleukin (IL)-33 induce bone pathology but absence of IL-33 does not negatively impact normal bone homeostasis.

Autor: Okragly AJ; Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA., Hamang MJ; Musculoskeletal-Biology, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA., Pena EA; Musculoskeletal-Biology, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA., Baker HE; Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA., Bullock HA; Musculoskeletal-Biology, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA., Lucchesi J; Musculoskeletal-Biology, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA., Martin AP; Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA., Ma YL; Musculoskeletal-Biology, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA., Benschop RJ; Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: benschop_robert@lilly.com.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2016 Mar; Vol. 79, pp. 66-73. Date of Electronic Publication: 2016 Jan 06.
DOI: 10.1016/j.cyto.2015.12.011
Abstrakt: Interleukin (IL)-33 is a member of the IL-1 family. IL-33 effects are mediated through its receptor, ST2 and IL-1RAcP, and its signaling induces the production of a number of pro-inflammatory mediators, including TNFα, IL-1β, IL-6, and IFN-γ. There are conflicting reports on the role of IL-33 in bone homeostasis, with some demonstrating a bone protective role for IL-33 whilst others show that IL-33 induces inflammatory arthritis with concurrent bone destruction. To better clarify the role IL-33 plays in bone biology in vivo, we studied IL-33 KO mice as well as mice in which the cytokine form of IL-33 was overexpressed. Mid-femur cortical bone mineral density (BMD) and bone strength were similar in the IL-33 KO mice compared to WT animals during the first 8months of life. However, in the absence of IL-33, we observed higher BMD in lumbar vertebrae and distal femur in female mice. In contrast, overexpression of IL-33 resulted in a marked and rapid reduction of bone volume, mineral density and strength. Moreover, this was associated with a robust increase in inflammatory cytokines (including IL-6 and IFN-γ), suggesting the bone pathology could be a direct effect of IL-33 or an indirect effect due to the induction of other mediators. Furthermore, the detrimental bone effects were accompanied by increases in osteoclast number and the bone resorption marker of C-terminal telopeptide collagen-I (CTX-I). Together, these results demonstrate that absence of IL-33 has no negative consequences in normal bone homeostasis while high levels of circulating IL-33 contributes to pathological bone loss.
(Copyright © 2015 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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