NDLI: Transglutaminase 2 up-regulation is associated with RANKL/OPG pathway in cultured HPDL cells and THP-1-differentiated macrophages

Content Provider	Springer Nature Link
Author	Matarese, Giovanni Currò, Monica Isola, Gaeta Caccamo, Daniela Vecchio, Mercurio Giunta, Maria Laura Ramaglia, Luca Cordasco, Giancarlo Williams, Ray C. Ientile, Riccardo
Copyright Year	2015
Abstract	Recent evidence emphasized that transglutaminase 2 (TG2), a protein cross-linking enzyme, may play a role in the early phase of inflammation. High levels of TG2 have been associated with the constitutive activation of nuclear factor-kappa B (NF-κB) that is considered the main regulator of inflammation. In this context, the receptor activator of NF-kappa B ligand (RANKL) and receptor activator of NF-κB have extensive functions in the regulation of cytokine secretion associated with different pathological conditions. The human periodontal ligament (HPDL) cells, which express and secrete osteoprotegerin (OPG) and RANKL, represent an useful “ex vivo” model for monitoring cell response in inflammatory microenvironments, such as periodontitis-dependent tissue response. Thus, we evaluated TG2 expression and alterations in RANKL/OPG ratio occurring in cultured HPDL cells. The HPDL cells were obtained from patients with chronic periodontitis (CP) and healthy subjects. We observed the up-regulation of some inflammatory markers, such as IL-6, TNF-α, and HMGB-1, and at the same time an increase in TG2 mRNA levels in HPDL cells from CP patients compared with healthy subjects. We found a positive correlation between RANKL/OPG ratio and TG2 mRNA levels in HPDL cells from CP patients. In the parallel experiments, we demonstrated that TG2 inhibition reduced RANKL expression in both HPDL cells from CP patients and monocytes differentiated to macrophages by tetradecanoyl phorbol acetate treatment. Given the RANKL key role in NF-κB pathway and the observed up-regulation of pro-inflammatory cytokines, our data suggest that TG2 may be involved in molecular mechanisms of inflammatory response occurring in periodontal disease.
Starting Page	2447
Ending Page	2455
Page Count	9
File Format	PDF
ISSN	09394451
Journal	Amino Acids
Volume Number	47
Issue Number	11
e-ISSN	14382199
Language	English
Publisher	Springer Vienna
Publisher Date	2015-07-02
Publisher Place	Vienna
Access Restriction	Subscribed
Subject Keyword	RANKL/OPG Chronic periodontitis Transglutaminase Monocytes/macrophages Inflammation Human periodontal fibroblasts Biochemistry Analytical Chemistry Biochemical Engineering Life Sciences Proteomics Neurobiology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry Clinical Biochemistry

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