BACKGROUND/AIMS: Chemokines are small chemotactic molecules which regulate the infiltration of immune cells to sites of inflammatory injury. In recent years their contribution to the initiation and perpetuation of liver injury has been better defined. However, the role of chemokines in liver diseases related to the metabolic syndrome still needs to be elucidated in detail. METHODS: Chemokines were mostly detected at the mRNA level in the liver and as proteins in the serum of patients with non-alcoholic steatohepatitis (NASH) or fatty liver. Animals with targeted deletion of chemokines have recently been subjected to NASH models to functionally dissect the role of chemokines in fatty liver diseases. RESULTS: In human liver with features of NASH, different CC and CXC chemokines have been detected at elevated mRNA levels in comparison to healthy subjects. Some of these chemokines have also been associated with NASH by demonstrating higher serum levels in affected patients. Until now, only a few animal models have been analyzed with respect to the functional role of these molecules. However, data from CCL2 and CXCR3 knockout mice suggest that these pathways are important in liver injury. CCL2 seems to influence the infiltration of macrophages to adipose tissue and thereby modulate insulin resistance. CONCLUSIONS: The further elucidation of the pathophysiology of NASH will lead to new therapeutic options to halt or reverse progressive liver disease. In this respect, chemokines are attractive target molecules, as they influence immunologic and metabolic pathways and the first oral chemokine receptor antagonists have already been licensed for humans. Copyright 2010 S. Karger AG, Basel.
BACKGROUND/AIMS: Chemokines are small chemotactic molecules which regulate the infiltration of immune cells to sites of inflammatory injury. In recent years their contribution to the initiation and perpetuation of liver injury has been better defined. However, the role of chemokines in liver diseases related to the metabolic syndrome still needs to be elucidated in detail. METHODS: Chemokines were mostly detected at the mRNA level in the liver and as proteins in the serum of patients with non-alcoholic steatohepatitis (NASH) or fatty liver. Animals with targeted deletion of chemokines have recently been subjected to NASH models to functionally dissect the role of chemokines in fatty liver diseases. RESULTS: In human liver with features of NASH, different CC and CXC chemokines have been detected at elevated mRNA levels in comparison to healthy subjects. Some of these chemokines have also been associated with NASH by demonstrating higher serum levels in affected patients. Until now, only a few animal models have been analyzed with respect to the functional role of these molecules. However, data from CCL2 and CXCR3 knockout mice suggest that these pathways are important in liver injury. CCL2 seems to influence the infiltration of macrophages to adipose tissue and thereby modulate insulin resistance. CONCLUSIONS: The further elucidation of the pathophysiology of NASH will lead to new therapeutic options to halt or reverse progressive liver disease. In this respect, chemokines are attractive target molecules, as they influence immunologic and metabolic pathways and the first oral chemokine receptor antagonists have already been licensed for humans. Copyright 2010 S. Karger AG, Basel.
Authors: Shijie Li; Paul Kievit; Anna-Karin Robertson; Ganesh Kolumam; Xiumin Li; Karin von Wachenfeldt; Christine Valfridsson; Sherry Bullens; Ilhem Messaoudi; Lindsay Bader; Kyra J Cowan; Amrita Kamath; Nicholas van Bruggen; Stuart Bunting; Björn Frendéus; Kevin L Grove Journal: Mol Metab Date: 2013-06-11 Impact factor: 7.422
Authors: Tania M Welzel; Barry I Graubard; Stefan Zeuzem; Hashem B El-Serag; Jessica A Davila; Katherine A McGlynn Journal: Hepatology Date: 2011-06-30 Impact factor: 17.425
Authors: Y Wang; E T Parlevliet; J J Geerling; S J L van der Tuin; H Zhang; V Bieghs; A H M Jawad; R Shiri-Sverdlov; I Bot; S C A de Jager; L M Havekes; J A Romijn; K Willems van Dijk; P C N Rensen Journal: Br J Pharmacol Date: 2014-02 Impact factor: 8.739
Authors: Leonardo G Da Fonseca; Pedro H Hashizume; Irai Santana de Oliveira; Laura Izquierdo-Sanchez; Lisa Rodrigues da Cunha Saud; Mariana Pinheiro Xerfan; Venancio Avancini Ferreira Alves; Evandro Sobroza de Mello; Paulo Herman; Jesus M Banales; Claudia P Oliveira; Flair J Carrilho Journal: Cancers (Basel) Date: 2022-07-18 Impact factor: 6.575