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The systemic exercise-released chemokine lymphotactin/XCL1 modulates in vitro adult hippocampal precursor cell proliferation and neuronal differentiation.

ABSTRACT: Physical exercise has well-established anti-inflammatory effects, with neuro-immunological crosstalk being proposed as a mechanism underlying the beneficial effects of exercise on brain health. Here, we used physical exercise, a strong positive modulator of adult hippocampal neurogenesis, as a model to identify immune molecules that are secreted into the blood stream, which could potentially mediate this process. Proteomic profiling of mouse plasma showed that levels of the chemokine lymphotactin (XCL1) were elevated after four days of running. We found that XCL1 treatment of primary cells isolated from both the dentate gyrus and the subventricular zone of the adult mice led to an increase in the number of neurospheres and neuronal differentiation in neurospheres derived from the dentate gyrus. In contrast, primary dentate gyrus cells isolated from XCL1 knockout mice formed fewer neurospheres and exhibited a reduced neuronal differentiation potential. XCL1 supplementation in a dentate gyrus-derived neural precursor cell line promoted neuronal differentiation and resulted in lower cell motility and a reduced number of cells in the S phase of the cell cycle. This work suggests an additional function of the chemokine XCL1 in the brain and underpins the complexity of neuro-immune interactions that contribute to the regulation of adult hippocampal neurogenesis.

SUBMITTER: Leiter O

PROVIDER: S-EPMC6694144 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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The systemic exercise-released chemokine lymphotactin/XCL1 modulates in vitro adult hippocampal precursor cell proliferation and neuronal differentiation.

Leiter Odette O Bernas Stefanie N SN Seidemann Suse S Overall Rupert W RW Horenburg Cindy C Kowal Susann S Kempermann Gerd G Walker Tara L TL

Scientific reports 20190814 1

Physical exercise has well-established anti-inflammatory effects, with neuro-immunological crosstalk being proposed as a mechanism underlying the beneficial effects of exercise on brain health. Here, we used physical exercise, a strong positive modulator of adult hippocampal neurogenesis, as a model to identify immune molecules that are secreted into the blood stream, which could potentially mediate this process. Proteomic profiling of mouse plasma showed that levels of the chemokine lymphotacti ...[more]

PMID: 31413355

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Project description:Periprosthetic osteolysis induced by orthopedic implant-wear particles continues to be the leading cause of arthroplasty failure in majority of patients. Release of the wear debris results in a chronic local inflammatory response typified by the recruitment of immune cells, including macrophages. The cellular mediators derived from activated macrophages favor the osteoclast-bone resorbing activity resulting in bone loss at the site of implant and loosening of the prosthetic components. Emerging evidence suggests that chemokines and their receptors are involved in the progression of periprosthetic osteolysis associated with aseptic implant loosening. In the current study, we investigated the potential role of chemokine C-motif-ligand-1 (XCL1) in the pathogenesis of inflammatory osteolysis induced by wear particles. Expressions of XCL1 and its receptor XCR1 were evident in synovial fluids and tissues surrounding hip-implants of patients undergoing revision total hip arthroplasty. Furthermore, murine calvarial osteolysis model induced by ultra-high molecular weight polyethylene (UHMWPE) particles was used to study the role of XCL1 in the development of inflammatory osteolysis. Mice received single injection of recombinant XCL1 onto the calvariae after implantation of particles exhibited significantly greater osteolytic lesions than the control mice. In contrast, blockade of XCL1 by neutralizing antibody significantly reduced bone erosion and the number of bone-resorbing mature osteoclasts induced by UHMWPE particles. In consistence with the results, transplantation of XCL1-soaked sponge onto calvariae caused osteolytic lesions coincident with excessive infiltration of inflammatory cells and osteoclasts. These results suggested that XCL1 might be involved in the development of periprosthetic osteolysis through promoting infiltration of inflammatory cells and bone resorbing-osteoclasts. Our further results demonstrated that supplementing recombinant XCL1 to cultured human monocytes stimulated with the receptor activator of nuclear factor kappa-B ligand (RANKL) promoted osteoclastogenesis and the osteoclast-bone resorbing activity. Moreover, recombinant XCL1 promoted the expression of inflammatory and osteoclastogenic factors, including IL-6, IL-8, and RANKL in human differentiated osteoblasts. Together, these results suggested the potential role of XCL1 in the pathogenesis of periprosthetic osteolysis and aseptic loosening. Our data broaden knowledge of the pathogenesis of aseptic prosthesis loosening and highlight a novel molecular target for therapeutic intervention.

Dataset Information

The systemic exercise-released chemokine lymphotactin/XCL1 modulates in vitro adult hippocampal precursor cell proliferation and neuronal differentiation.

Publications

The systemic exercise-released chemokine lymphotactin/XCL1 modulates in vitro adult hippocampal precursor cell proliferation and neuronal differentiation.

Similar Datasets

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