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Published on: July 17, 2018
Chemokine Expression during Adipogenesis and Inflammation in Orbital Fibroblasts from Patients with Graves'
Chae Eun Lee1, Soo Hyun Choi2, Jin Sook Yoon3
1Yonsei University College of Medicine, Seoul, Korea.
Purpose:
Chemokines are involved in the pathogenesis of various autoimmune diseases, including Graves' orbitopathy (GO), but comprehensive analyses of the dynamics of these cytokines and their receptors in such diseases remain lacking. In this study, we investigated the expressions of chemokines and their receptors during adipogenesis and inflammation in primary cultured orbital fibroblasts from patients with GO.
Methods:
The messenger RNA (mRNA) expression levels of chemokines were compared between GO (n = 6) and non-GO (n = 5) orbital tissues by real-time polymerase chain reaction. After adipogenesis was induced in primary cultured orbital fibroblasts from patients with GO (n =5) and following stimulation with interleukin (IL)-1β and tumor necrosis factor (TNF)-α, the mRNA expression levels of chemokines and their receptors were analyzed.
Results:
Chemokines were significantly downregulated in GO orbital tissues compared to non-GO orbital tissues (p < 0.05). Adipogenesis resulted in a strong increase in mRNA expression levels of chemokines and their receptors at an early stage (day 1); however, expression levels started to decrease thereafter and, eventually, decreased to below basal levels at the end of adipogenesis (day 10). Following stimulation with IL-1β and TNF-α, the mRNA expression levels of chemokines and their receptors increased, showing different responses to various proinflammatory cytokines.
Conclusions:
Chemokines were strongly upregulated in the early phase of adipogenesis before decreasing continuously until the end of adipogenesis. Also, overt mature GO tissues showed reduced mRNA expression of chemokines compared to controls, which might indicate the existence of a shorter window for effective medical inflammatory treatment. The heightened levels of chemokines and their receptors observed after stimulation with IL-1β and TNF-α suggest a crucial role of proinflammatory cytokines in the pathogenesis of GO and, further, support the idea that chemokines could be used as biomarkers of GO activity.
Insights
Chemokines are downregulated in Graves' orbitopathy (GO) tissues. Their expression changes during adipogenesis and inflammation, suggesting a role in GO pathogenesis and potential use as biomarkers.
Area of Science:
- Immunology
- Endocrinology
- Ophthalmology
Background:
- Chemokines mediate autoimmune disease pathogenesis.
- Graves' orbitopathy (GO) is an autoimmune condition affecting the eye.
- Limited data exists on chemokine dynamics in GO.
Purpose of the Study:
- Investigate chemokine and receptor expression in GO.
- Analyze dynamics during orbital fibroblast adipogenesis and inflammation.
Main Methods:
- Compared mRNA expression of chemokines in GO vs. non-GO orbital tissues (real-time PCR).
- Induced adipogenesis in primary GO orbital fibroblasts.
- Stimulated fibroblasts with IL-1β and TNF-α.
- Analyzed chemokine and receptor mRNA expression.
Main Results:
- Chemokines were downregulated in GO tissues (p < 0.05).
- Adipogenesis initially increased chemokine/receptor mRNA, then decreased.
- IL-1β and TNF-α stimulation upregulated chemokines/receptors.
Conclusions:
- Chemokines show dynamic expression during adipogenesis and inflammation in GO.
- Reduced chemokine expression in GO tissues may indicate a therapeutic window.
- Chemokines and receptors are implicated in GO pathogenesis and could be GO biomarkers.
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