TIMP-1 Mediates Inflammatory and Immune Response to IL-6 in Adult Orbital Xanthogranulomatous Disease

Abstract

Purpose: To explore the pathogenesis that TIMP-1 mediated in adult orbital xanthogranulomatous disease (AOXGD), a rare type of non-Langerhans histiocytosis that damages the appearance and quality of life of patients

Methods: We reviewed 22 patients diagnosed with AOXGD based on clinical manifestations and histological analysis, and then investigated the expression of TIMP-1 and IL-6 with q-PCR and IHC in AOXGD tissues and the possible mechanism involved in the induction of TIMP-1 by IL-6.

Results: IL-6 and TIMP-1 were significantly increased in AOXGD tissues. IL-6 promoted TIMP-1 production by M1 macrophages by stimulating the phosphorylation of JAK2 and STAT3. Moreover, IL-17 and IFN-γ, the classical markers of Th1 and Th17 cells, were increased in AOXGD.

Conclusion: These data implied that the IL6~JAK2/STAT3-TIMP-1 signalling pathway is activated in AOXGD and that adaptive Th1 and Th17 responses are involved in the development of AOXGD.

Keywords:

• adult orbital xanthogranulomatous disease
• IL-6
• TIMP-1

DECLARATION OF INTEREST

The authors declare no competing financial interests.

ACKNOWLEDGMENTS

The study was performed according to the principles of the Declaration of Helsinki and Shanghai Ninth People’s hospital Committee approved the study. Informed consent about tissue samples and photographs were obtained.

AUTHOR CONTRIBUTIONS

In our study, Xia Ding drafted the manuscript, Yuan Cao and Yue Xing collected and analysed the data and photographs, Shengfang Ge and Ming Lin designed the study and interpreted the data, Jin Li revised and decided to submit the manuscript.

Additional information

Funding

The study was supported by the National Natural Science Foundation of China (grants 81870688 and 81602525), the Science and Technology Commission of Shanghai Municipality (grants 16ZR1419600 and 17DZ2260100).