A reporter mouse for non-invasive detection of toll-like receptor ligands induced acute phase responses

Abstract

The acute phase response (APR) is a systemic first-line defense against challenges including infection, trauma, stress, and neoplasia. Alteration of acute phase protein (APP) levels in plasma is the most important change during acute phase response. C-reactive protein (CRP), which increases dramatically during inflammation onset, is an indicator of inflammation. To monitor the process of APR, we generated human CRP promoter-driven luciferase transgenic (hCRP-Luc) mice to quantify the hCRP promoter activation in vivo. The naïve female hCRP-Luc mice express low basal levels of liver bioluminescence, but the naïve male hCRP-Luc mice do not. Thus, female hCRP-Luc mice are suitable for monitoring the process of APR. The liver bioluminescence of female hCRP-Luc mice can be induced by several toll-like receptor (TLR) ligands. The expression of liver bioluminescence was highly sensitive to endotoxin stimulation in a dose-dependent manner. On-off-on bioluminescence response was noted in female hCRP-Luc mice upon two endotoxin stimulations one month apart. The LPS-induced bioluminescence of the female hCRP-Luc mice was IL-6-mediated and associated with APP alpha-1-acid glycoprotein expression. In conclusion, the female hCRP-Luc mouse is a non-invasive, sensitive and reusable reporter tool for APR.

Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant

“…IL-6 and C-reactive protein (CRP) are commonly used as systemic inflammatory mediators and their serum levels are highly associated with systemic reactogenicity of vaccines in humans [21]. Due to the significant baseline serum CRP levels in mice [22], we selectively measured serum IL-6 levels 3 and 18 h after immunization. As shown in Figure 4A, prime NP/M1 immunization significantly increased serum IL-6 levels at 3 hours and incorporation of RFA failed to significantly increase serum IL-6 levels.…”

The Human Milk Oligosaccharide 3’Sialyllactose Promotes Inflammation Resolution and Reduces Atherosclerosis Development in Mice

“…SAA is an acute phase protein, and its plasma levels correlate with atherosclerotic development in mice and humans 63 . In mice, SAA serves as a proxy for the human atherogenic hsCRP, as CRP in mice is only a modest acute phase protein 64 . Oral 3’SL treatment was associated with significantly reduced plasma SAA levels after two and six weeks of treatment, by 2.3- and 2.8- fold respectively, compared to control treated Ldlr -/- mice (Fig.…”

The human milk oligosaccharide 3’sialyllactose promotes inflammation resolution and reduces atherosclerosis development.

“…The more profound antiatherogenic effect induced by oral administration was also associated with a strong reduction of systemic inflammation. The observation that SAA went down a great deal upon oral 3'SL treatment is strong evidence for systemic decrease in inflammation as SAA is mainly made in the liver 64 . These favorable antiatherogenic discrepancy between the two administration routes could be a result of alterations in the microbiome in the gastrointestinal tract or due to a first pass effect of oral administered 3'SL via the liver, where the majority of the measured cytokines and triglyceride-rich lipoproteins are produced and cleared.…”

“…SAA is an acute phase protein, and its plasma levels correlate with atherosclerotic development in mice and humans 63 . In mice, SAA serves as a proxy for the human atherogenic hsCRP, as CRP in mice is only a modest acute phase protein 64 . Oral 3'SL treatment was associated with significantly reduced plasma SAA levels after two and six weeks of treatment, by 2.3-and 2.8fold respectively, compared to control treated Ldlr -/mice (Fig.…”