Sj?gren’s syndrome (SS) is a chronic autoimmune disorder of the exocrine
glands with clinical manifestation of dry eyes and dry mouth. The pathogenesis
of SS is poorly understood, and efficient therapy is currently lacking. Therefore,
an appropriate animal model recapitulating the key features of SS could be of
profound value. Although several murine models have been established and
evaluated, some of these models may develop other non-SS symptoms
simultaneously. Herein, an autoimmunization-induced C57BL/6 female mouse
model is evaluated. This mouse model exhibited less saliva secretion and
swollen salivary gland with severe inflammation in the submandibular gland.
Furthermore, apoptosis and pro-inflammatory cytokines were significantly
increased and the expression of aquaporin 5, a water channel protein, was
decreased and restricted to the basolateral membranes in acinar cells, indicating
the weakening of water transport. Besides, autoantibodies such as Ro, La and
other anti-nuclear autoantigens were found to be tremendously increased. The
expression of M3 muscarinic receptor (M3R) increased in the acinar cells. This
can be described as a compensatory expression due to the long term blockage
from the autoantibodies which is similar in the SS patients. The characteristics
of this model recapitulate the key features of human SS. Dendrobium officinale
is an herbal medicine with yin-nourishing effect and clinically used in China as
a health tonic to promote body fluid production. The polysaccharides extracted
from Dendrobium officinale (DP) consisted of 6 monosaccharides: mannose,
glucose, galactose, arabinose, xylose and glucuronic acid in the ratio of
10:0.25:1.2:4.7:1.3:1.4. DP was found to be protective on this experimental SS
model. Specifically, administration of DP 20 mg/ml significantly prevented the
chaos of immune responses and imbalance of pro-inflammatory cytokines. Our
previous work also demonstrated that DP can promote saliva production in both
SS patients and SS model. Therefore, we investigated the M3R activation
induced by DP treatment. In contrast to the acute activation by acetylcholine, DP
exerts slow, but long term activation on M3R. The botanical monosaccharides
xylose and arabinose cannot be detected in the cell lysate, indicating that
hydrolyzed DP did not permeate the cell membrane. Further investigations
suggested that DP can inhibit the apoptosis induced by the addition of
recombinant TNF-α on the human salivary gland epithelial cell line A-253. By
investigating the potential mechanisms, we found that DP treatment can inhibit
the apoptotic factors including the NF-κB activation, increased reactive oxygen
species, decreased mitochondrial membrane potential and prolonged
mitogen-activated protein kinase activation. The results suggested that DP may
interfere with the TNF-α pathway and its receptor since DP did not permeate the
cell membrane. / published_or_final_version / Chinese Medicine / Doctoral / Doctor of Philosophy
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/161522 |
| Date | January 2011 |
| Creators | Lin, Xiang, 林响 |
| Contributors | Zhang, Y, Zhang, Z, Sze, CW |
| Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
| Source Sets | Hong Kong University Theses |
| Language | English |
| Detected Language | English |
| Type | PG_Thesis |
| Source | http://hub.hku.hk/bib/B47869628 |
| Rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works., Creative Commons: Attribution 3.0 Hong Kong License |
| Relation | HKU Theses Online (HKUTO) |
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