TY  - GEN
A1  - Nojima, Hiroyuki
A1  - Konishi, Takanori
A1  - Freeman, Christopher M.
A1  - Schuster, Rebecca M.
A1  - Japtok, Lukasz
A1  - Kleuser, Burkhard
A1  - Edwards, Michael J.
A1  - Gulbins, Erich
A1  - Lentsch, Alex B.
T1  - Chemokine receptors, CXCR1 and CXCR2, differentially regulate exosome release in hepatocytes
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Exosomes are small membrane vesicles released by different cell types, including hepatocytes, that play important roles in intercellular communication. We have previously demonstrated that hepatocyte-derived exosomes contain the synthetic machinery to form sphingosine-1-phosphate (S1P) in target hepatocytes resulting in proliferation and liver regeneration after ischemia/reperfusion (I/R) injury. We also demonstrated that the chemokine receptors, CXCR1 and CXCR2, regulate liver recovery and regeneration after I/R injury. In the current study, we sought to determine if the regulatory effects of CXCR1 and CXCR2 on liver recovery and regeneration might occur via altered release of hepatocyte exosomes. We found that hepatocyte release of exosomes was dependent upon CXCR1 and CXCR2. CXCR1-deficient hepatocytes produced fewer exosomes, whereas CXCR2-deficient hepatocytes produced more exosomes compared to their wild-type controls. In CXCR2-deficient hepatocytes, there was increased activity of neutral sphingomyelinase (Nsm) and intracellular ceramide. CXCR1-deficient hepatocytes had no alterations in Nsm activity or ceramide production. Interestingly, exosomes from CXCR1-deficient hepatocytes had no effect on hepatocyte proliferation, due to a lack of neutral ceramidase and sphingosine kinase. The data demonstrate that CXCR1 and CXCR2 regulate hepatocyte exosome release. The mechanism utilized by CXCR1 remains elusive, but CXCR2 appears to modulate Nsm activity and resultant production of ceramide to control exosome release. CXCR1 is required for packaging of enzymes into exosomes that mediate their hepatocyte proliferative effect.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 538 
KW  - hepatic ischemia-reperfusion
KW  - liver-regeneration
KW  - injury
KW  - ischemia/reperfusion
KW  - neutrophil
KW  - ceramide
KW  - homolog
KW  - mice
KW  - mechanisms
KW  - recovery
Y1  - 2019
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/41088
UR  - https://nbn-resolving.org/urn:nbn:de:kobv:517-opus4-410885
SN  - 1866-8372
IS  - 538
ER  -