Abstract
Purpose: :
Several cytokines and chemokines, including IL-1β and IL-10, have been shown to be upregulated in patients with Sjogren’s Syndrome (SS). However, the time course in cytokine and chemokine changes in SS remains to be elucidated. We have been studying disease progression using ovariectomized NOD.B10-H2b mice, which provides a model of menopause combined with a predisposed genetic background to SS. Previously, using our model, we have shown an increase in the protein levels of IL-1β, IL-10 and CCL9 seven days post-ovx. This present study represents further investigation of the changes in the levels of cytokines and chemokines at different time points in ovariectomized NOD.B10-H2b mice.
Methods: :
Six wks old C57BL/10SnJ, control and NOD.B10-H2b, mouse model of SS, were ovariectomized (OVX) or sham operated. After 3, 7 or 21 days, the lacrimal glands were removed, pooled and homogenized. Total RNA was used to analyze gene expression levels and ELISA analysis was used to determine protein concentration of IL-1β, IL-10 and CCL9.
Results: :
Ovariectomized NOD mice showed increases in both gene expression and protein levels of IL-1β, IL-10 and CCL9 at 7 days post-ovx. However, at 21 days post-ovx, only IL-10 was shown to be upregulated at both gene and protein levels in the lacrimal glands of NOD.B10-H2b mice. No significant changes were seen in the gene expression or protein levels of the above mentioned cytokines and chemokines between the sham and OVX in the C57BL/10SnJ mice at any of the experimental time points.
Conclusions: :
Our results suggest that in earlier stages of disease progression there is an upregulation of proinflammatory cytokine, IL-1β, as well as anti-inflammatory cytokine, IL-10. However, as time progresses only IL-10 remains increased. These results may suggest that IL-10 can cause a down-regulation of the Th1 response.
Keywords: lacrimal gland • cytokines/chemokines • autoimmune disease