Diabetes mellitus (DM) is the 4th leading cause of mortality in
Taiwan. Chronic persistent inflammation as demonstrated by higher
proinflammatory mediators in blood has been correlated to cardiovascular
complications of type 2 DM. The cellular and molecular mechanism of
chronic inflammation in type 2 DM remains to be determined. This study
was conducted to explore altered innate immunity in toll-like receptor
(TLR) expression and signaling of monocytes from type 2 DM patients.
Blood leukocytes from type 2 DM patients were counted and studied for
TLR2 and TLR4 expression and signaling. Each experiment was run with
1 to 2 type 2 DM patients, simultaneously with 1 to 2 age-matched
normal adults as controls. 31 type 2 DM patients and 37 normal
age-matched controls completed the study. Results showed that blood
monocytes from type 2 DM patients had a significantly higher TLR4 but
not TLR2 expression. Using a TLR4 ligand, lipopolysaccharide (LPS), to
trigger TNF£\ production, a significantly higher TNF£\ production by
blood leukocytes from type 2 DM patients than age-matched controls was
found. The higher TNF£\ production by blood leukocytes from type 2 DM
patients was associated with down-regulation of suppressor of cytokine
signaling 1and 3 (SOCS-1 and SOCS-3) expression. We have further
postulated that increase of oxidative stress or decrease of
IFN-£\ production in type 2 DM patients was related to the alteration of
TLR-4 response. Correction of SOCS-1 expression by addition of
antioxidant, superoxide dismutase (SOD), but not IFN-£\, significantly
decreased TNF£\ production in blood leukocytes from type 2 DM patients.
This study is the first in the literature to identify an alteration of TLR4
expression associated with depressed SOCS-1 expression in leukocytes of
type 2 DM patients. Results from this study highlight a potential pathway
to improve chronic inflammation of type 2 DM patients via modulation of
TLR4 expression and SOCS-1 mRNA expression of leukocytes.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0622106-154652 |
| Date | 22 June 2006 |
| Creators | Chuang, Hua |
| Contributors | none, Kuender-D Yang, Jiin-Tsuey Cheng, Rue-Tsuan Liu |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0622106-154652 |
| Rights | withheld, Copyright information available at source archive |
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