Previous studies have demonstrated that bacterial lipopolysaccharide (LPS) and heat killed Staphylococcus aureus (SA) activation of inflammatory cells depended in part upon activation of heterotrimeric Gi proteins. It has also been shown that (1→3) beta-D-glucan can suppress inflammatory cell activation by microbial products although the cellular mechanism of the glucan effect remains to be clearly defined. We hypothesized that Gi proteins function as a common convergent signaling pathway for both LPS and SA leading to monocyte mediator production. Additionally, we hypothesized that soluble glucan suppresses LPS and SA induced cytokine production via Gi protein coupled signaling. Human THP-1 promonocytic cells were pretreated with pertussis toxin (PTx, 100ng/ml or 1 microgram/ml) 6 hours prior to stimulation with LPS (10 microgram/ml) and SA (10 microgram/ml) and/or soluble glucan (10 microgram/ml). Both LPS and SA significantly (p<0.05) induced cytokine production IL-6 >TNF alpha >IL-1 beta >GM-CSF >IL-10 >IFN gamma. The induction of these cytokines was significantly (p<0.05) suppressed by PTx. Glucan treatment alone had no effect on cytokine production but suppressed (P<0.05) LPS and SA induced cytokines. PTx further augmented (p<0.05) the inhibitory effect of glucan on the LPS and SA induced cytokine expression. The data support the hypothesis that Gi proteins function as a common signaling protein for both LPS and SA induction of pro-and anti-inflammatory cytokines and that soluble glucan effectively suppresses cytokine production to the microbial stimuli. In contrast, the effect of soluble glucan on inhibiting cellular activation by LPS and SA is Gi protein independent.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-19539 |
| Date | 08 June 2006 |
| Creators | Fan, Hongkuan, Williams, David L., Breuel, Kevin F., Zingarelli, Basilia, Teti, Giuseppe, Tempel, George E., Halushka, Perry V., Cook, James A. |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
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