Proinflammatory Effects of Calprotectin in Graves’ Orbitopathy

ABSTRACT

Purpose: Early detection and control of inflammation are important to manage Graves’ orbitopathy (GO). We investigated the effects of calprotectin (S100A8/A9) on orbital fibroblast inflammation and GO pathogenesis.

Methods: We measured serum calprotectin, S100A8 and S100A9 mRNA expression in orbital fat/connective tissue from GO patients and healthy controls, and proinflammatory cytokines in primary cultured orbital fibroblasts.

Results: The serum levels of S100A8/A9 and the expression of S100A8/A9 mRNA in orbital tissue were higher in the GO patients than in the healthy controls. The serum calprotectin levels positively correlated with the clinical activity score and serum thyroid-stimulating immunoglobulin levels. In cultured GO orbital fibroblasts, S100A8/A9 increased the expression of interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1, as well as the phosphorylation of extracellular signal-regulated kinase and nuclear factor-κB.

Conclusion: We demonstrated the potential of calprotectin as a biomarker of GO severity and proinflammatory responses to S100A8/A9 in GO orbital fibroblasts.

Keywords:

• Calprotectin
• Graves’ orbitopathy
• inflammation
• orbital fibroblast
• thyroid eye disease

Disclosure of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of science and ICT [NRF-2017R1A2B4009565].