P2Y 2 R deletion ameliorates sialadenitis in IL-14α-transgenic mice.

Autor: Woods LT; Department of Biochemistry, University of Missouri, Columbia, MO, USA.; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA., Camden JM; Department of Biochemistry, University of Missouri, Columbia, MO, USA.; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA., Khalafalla MG; Department of Biochemistry, University of Missouri, Columbia, MO, USA.; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA., Petris MJ; Department of Biochemistry, University of Missouri, Columbia, MO, USA.; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.; Department of Nutritional Sciences and Exercise Physiology, University of Missouri, Columbia, MO, USA., Erb L; Department of Biochemistry, University of Missouri, Columbia, MO, USA.; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA., Ambrus JL Jr; Department of Medicine, Division of Allergy, Immunology and Rheumatology, SUNY at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA., Weisman GA; Department of Biochemistry, University of Missouri, Columbia, MO, USA.; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.
Jazyk: angličtina
Zdroj: Oral diseases [Oral Dis] 2018 Jul; Vol. 24 (5), pp. 761-771. Date of Electronic Publication: 2018 Mar 13.
DOI: 10.1111/odi.12823
Abstrakt: Objective: Interleukin-14α-transgenic (IL-14αTG) mice develop an autoimmune exocrinopathy with characteristics similar to Sjögren's syndrome, including sialadenitis and hyposalivation. The P2Y 2 receptor (P2Y 2 R) for extracellular ATP and UTP is upregulated during salivary gland inflammation (i.e., sialadenitis) where it regulates numerous inflammatory responses. This study investigated the role of P2Y 2 Rs in autoimmune sialadenitis in the IL-14αTG mouse model of Sjögren's syndrome.
Materials and Methods: IL-14αTG mice were bred with P2Y 2 R -/- mice to generate IL-14αTG × P2Y 2 R -/- mice. P2Y 2 R expression, lymphocytic focus scores, B- and T-cell accumulation, and lymphotoxin-α expression were evaluated in the submandibular glands (SMG) along with carbachol-stimulated saliva secretion in IL-14αTG, IL-14αTG × P2Y 2 R -/- , and C57BL/6 control mice at 9 and 12 months of age.
Results: Genetic ablation of P2Y 2 Rs in IL-14αTG mice significantly reduced B and T lymphocyte infiltration of SMGs. However, reduced sialadenitis did not restore saliva secretion in IL-14αTG × P2Y 2 R -/- mice. Decreased sialadenitis in IL-14αTG × P2Y 2 R -/- mice correlated with decreased lymphotoxin-α levels, a critical proinflammatory cytokine associated with autoimmune pathology in IL-14αTG mice.
Conclusions: The results of this study suggest that P2Y 2 Rs contribute to the development of salivary gland inflammation in IL-14αTG mice and may also contribute to autoimmune sialadenitis in humans.
(© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)
Databáze: MEDLINE
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