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Review
. 2018 Mar 10;10(1):1-16.
eCollection 2018.

New insights into Nod-like receptors (NLRs) in liver diseases

Tao Xu  1   2 , Yan Du  1   2 , Xiu-Bin Fang  3 , Hao Chen  1   2 , Dan-Dan Zhou  1   2 , Yang Wang  1   2 , Lei Zhang  1   2
Affiliations
Review

New insights into Nod-like receptors (NLRs) in liver diseases

Tao Xu et al. Int J Physiol Pathophysiol Pharmacol. .

Abstract

Activation of inflammatory signaling pathways is of central importance in the pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH). Nod-like receptors (NLRs) are intracellular innate immune sensors of microbes and danger signals that control multiple aspects of inflammatory responses. Recent studies demonstrated that NLRs are expressed and activated in innate immune cells as well as in parenchymal cells in the liver. For example, NLRP3 signaling is involved in liver ischemia-reperfusion (I/R) injury and silencing of NLRP3 can protect the liver from I/R injury. In this article, we review the evidence that highlights the critical importance of NLRs in the prevalent liver diseases. The significance of NLR-induced intracellular signaling pathways and cytokine production is also evaluated.

Keywords: NLRP3; Nod-like receptors (NLRs); liver diseases.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
The role of NOD1 in hepatocytes. Recognized by NOD1, C12-iEDAP can initiate NF-κB signaling and MAP kinases in hepatocytes, therefore inducing the expression of chemokines CXCL1 and CCL5, leading to augmentation of the adaptive immune response.
Figure 2
Figure 2
The role of NOD2 in immune cells. TNF-α and IFN-γ synergistically cooperate to induce NOD2 expression in hepatocyte cells. MDP recognition by NOD2 leads to activation of NF-κB and induces proinflammatory cytokine production by immune cells.
Figure 3
Figure 3
The function of NLRP3 in liver disease, with focus on cytokines.
See this image and copyright information in PMC

References

    1. Ni HM, Williams JA, Yang H, Shi YH, Fan J, Ding WX. Targeting autophagy for the treatment of liver diseases. Pharmacol Res. 2012;66:463–474. - PMC - PubMed
    1. Guicciardi ME, Malhi H, Mott JL, Gores GJ. Apoptosis and necrosis in the liver. Compr Physiol. 2013;3:977–1010. - PMC - PubMed
    1. Kern M, Popov A, Scholz K, Schumak B, Djandji D, Limmer A, Eggle D, Sacher T, Zawatzky R, Holtappels R, Reddehase MJ, Hartmann G, Debey-Pascher S, Diehl L, Kalinke U, Koszinowski U, Schultze J, Knolle PA. Virally infected mouse liver endothelial cells trigger CD8+ T-cell immunity. Gastroenterology. 2010;138:336–346. - PubMed
    1. Knolle PA, Gerken G. Local control of the immune response in the liver. Immunol Rev. 2000;174:21–34. - PubMed
    1. Knolle PA, Limmer A. Neighborhood politics: the immunoregulatory function of organ-resident liver endothelial cells. Trends Immunol. 2001;22:432–437. - PubMed

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