The Gut-Liver Axis: The Source of Inflammation in Acute and Chronic Diseases
Fatemeh Adiliaghdam, Florian Kuehn, Juan M. Ramirez, Robin Vasan, Enyu Liu, Yang Liu, Richard A. Hodin
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Background: Portal vein has a main role in gut-liver-systemic axis. This axis is affected in many diseases and leads to leaky-gut as an important inflammation source. Therefore,we hypothesized to determine proinflmamatory effect of portal vein in both acute and chronic disease models such as burn and aging. In parallel, to better approach to the portal vein role, we used intestinal alkaline phosphatase(IAP)KO mice as a leaky gut model.
Methods: C57BL/6 WT or IAP KO mice were used for 30% back burn and aging model. For assessment of proinflmamatory effect of portal serum, primary mouse macrophages were incubated with portal or systemic serum and inflammatory gene expression were measured.
Results: Interestingly,in all models portal serum showed significantly more proinflmamatory effect compared to systemic serum.(p<0.001) In burn model: there was a higher LPS in portal serum from burn group compared to the sham group(17.5versus4.8EU/L,p<0.01). In addition, portal serum from burned mice induced more TNFa and IL-B expression compared to sham group.(4fold change,p<0.01) Treatment of mice with IAP after burn decrease this proinflmamatory effect of portal serum.( p<0.01) In aging model: portal serum from 21months old mice showed more LPS level compared to 4months old one.(10.80versus5.10EU/L,p<0.05) Also portal serum from old mice showed significantly more proinflmamatory effect compared to young group.(p<0.01) Portal serum from IAP KO mice showed higher LPS level(15.8EU/L)and higher proinflmamatory effect compared to their WTs in both young and old animals.(p<0.05and<0.001,respectively)
Conclusion: Portal vein has a very high proinflmamatory characteristic in both acute and chronic disease. Targeting gut derived inflammation with IAP as anti-inflammatory factor could decrease this proinflmamatory effect of portal serum and represent a novel therapy to prevent gut-derived diseases.
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