title: Effects of blockade of peripheral interleukin-6 trans-signaling on hippocampus-dependent and independent memory in mice.
abstract: Besides functions of the interleukin-6 (IL-6)/gp130 cytokine family in immunology, IL-6 signaling has influence on memory processes. IL-6 acts on target cells via a membrane-bound IL-6 receptor (IL-6R) and subsequent association with the signal-transducing protein gp130. While gp130 is expressed on all cells in the body, IL-6R is expressed in only on few cells such as hepatocytes and some leukocytes. Cells lacking IL-6R were shown not to be responsive to the cytokine. Interestingly, a soluble form of the IL-6R in complex with IL-6 can stimulate cells that do not express the membrane-bound IL-6R. This signaling pathway has been called IL-6 trans-signaling. IL-6 trans-signaling can specifically be blocked by a soluble gp130 protein (sgp130Fc) without affecting IL-6 classic signaling via the membrane-bound IL-6R. Transgenic mice expressing sgp130Fc in the blood, but not in the central nervous system, were analyzed for hippocampus-dependent and independent memory, together with exploratory- and anxiety-related behavior. Transgenic animals did not show impaired hippocampus-dependent or independent learning and memory. However, compared to wild-type animals, they showed reduced exploratory behavior and an increased thermal pain threshold, indicating that these effects depend on IL-6 trans-signaling. These results bear important consequences for the therapeutic blockade of IL-6 activity in autoimmune diseases.
authors.affiliation: Department of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Braun
authors.forename: Christin
authors.initials: C
authors.lastname: Dewitz
authors.forename: Katja
authors.initials: K
authors.lastname: Möller-Hackbarth
authors.forename: Jürgen
authors.initials: J
authors.lastname: Scheller
authors.forename: Thomas
authors.initials: T
authors.lastname: Schiffelholz
authors.forename: Paul Christian
authors.initials: PC
authors.lastname: Baier
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
mesh_terms: D000818:Animals; D001775:Blood Circulation / Q000235:genetics; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017288:Pain Threshold / Q000502:physiology; D011485:Protein Binding; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130