Olfactory ensheathing cells moderate nuclear factor kappaB translocation in astrocytes

Hale, David; Ray, Shannon; Leung, J.; Holloway, Adele F.; Chung, Roger S.; West, Adrian K.; Chuah, Mi

doi:10.1016/j.mcn.2010.09.004

Cited by 12 publications

(7 citation statements)

References 72 publications

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“…As expected, NFκB increased in the nuclear fraction of immortalized C8D30 astrocytes treated with LPS (Figure 1A, gray bars, p ≤ .05). Co‐culture of astrocytes with OECs blocked nuclear translocation of NFκB in response to LPS, as previously reported (Hale et al, 2011; Figure 1A, purple bars). Adding CM from untreated OEC monocultures, (OEC‐CM), also decreased NFκB translocation into nuclei of astrocytes exposed to LPS (Figure 1A, red bars), indicating that anti‐inflammatory factor(s) are secreted by OECs even in the absence of a stress signal.…”

Section: Resultssupporting

confidence: 88%

Novel factor in olfactory ensheathing cell‐astrocyte crosstalk: Anti‐inflammatory protein α‐crystallin B

Saglam

Calof

Wray

2020

Glia

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Astrocytes are key players in CNS neuroinflammation and neuroregeneration that may help or hinder recovery, depending on the context of the injury. Although pro‐inflammatory factors that promote astrocyte‐mediated neurotoxicity have been shown to be secreted by reactive microglia, anti‐inflammatory factors that suppress astrocyte activation are not well‐characterized. Olfactory ensheathing cells (OECs), glial cells that wrap axons of olfactory sensory neurons, have been shown to moderate astrocyte reactivity, creating an environment conducive to regeneration. Similarly, astrocytes cultured in medium conditioned by cultured OECs (OEC‐CM) show reduced nuclear translocation of nuclear factor kappa‐B (NFκB), a pro‐inflammatory protein that induces neurotoxic reactivity in astrocytes. In this study, we screened primary and immortalized OEC lines to identify these factors and discovered that Alpha B‐crystallin (CryAB), an anti‐inflammatory protein, is secreted by OECs via exosomes, coordinating an intercellular immune response. Our results showed that: (a) OEC exosomes block nuclear NFκB translocation in astrocytes while exosomes from CryAB‐null OECs could not; (b) OEC exosomes could be taken up by astrocytes, and (c) CryAB treatment suppressed neurotoxicity‐associated astrocyte transcripts. Our results indicate CryAB, as well as other factors secreted by OECs, are potential agents that can ameliorate, or even reverse, the growth‐inhibitory environment created by neurotoxic reactive astrocytes following CNS injuries.

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Section: Resultssupporting

confidence: 88%

Novel factor in olfactory ensheathing cell‐astrocyte crosstalk: Anti‐inflammatory protein α‐crystallin B

Saglam

Calof

Wray

2020

Glia

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“…Olfactory ensheathing cells were isolated from the olfactory nerve layer of the olfactory bulb and the olfactory mucosa of 3-day-old mouse pups as described in a previous study [13]. Briefly, the olfactory bulbs and mucosa were dissected and digested for 20 min using 0.25% trypsin in MEM-H (Gibco) at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway

Herbert

Harris

Chong

et al. 2012

J Neuroinflammation

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BackgroundThe primary olfactory pathway is a potential route through which microorganisms from the periphery could potentially access the central nervous system. Our previous studies demonstrated that if the olfactory epithelium was damaged, bacteria administered into the nasal cavity induced nitric oxide production in olfactory ensheathing cells. This study investigates the cytokine profile of olfactory tissues as a consequence of bacterial challenge and establishes whether or not the bacteria are able to reach the olfactory bulb in the central nervous system.MethodsThe olfactory epithelium of C57BL/6 mice was damaged by unilateral Triton X-100 nasal washing, and Staphylococcus aureus was administered ipsilaterally 4 days later. Olfactory mucosa and bulb were harvested 6 h, 24 h and 5 days after inoculation and their cytokine profile compared to control tissues. The fate of S. aureus and the response of bulbar microglia were examined using fluorescence microscopy and transmission electron microscopy.ResultsIn the olfactory mucosa, administered S. aureus was present in supporting cells of the olfactory epithelium, and macrophages and olfactory nerve bundles in the lamina propria. Fluorescein isothiocyanate-conjugated S. aureus was observed within the olfactory mucosa and bulb 6 h after inoculation, but remained restricted to the peripheral layers up to 5 days later. At the 24-h time point, the level of interleukin-6 (IL-6) and tumour necrosis factor-α in the compromised olfactory tissues challenged with bacteria (12,466 ± 956 pg/ml and 552 ± 193 pg/ml, respectively) was significantly higher than that in compromised olfactory tissues alone (6,092 ± 1,403 pg/ml and 80 ± 2 pg/ml, respectively). Immunohistochemistry confirmed that IL-6 was present in several cell types including olfactory ensheathing cells and mitral cells of the olfactory bulb. Concurrently, there was a 4.4-, 4.5- and 2.8-fold increase in the density of iNOS-expressing cells in the olfactory mucosa, olfactory nerve and glomerular layers combined, and granule layer of the olfactory bulb, respectively.ConclusionsBacteria are able to penetrate the immunological defence of the compromised olfactory mucosa and infiltrate the olfactory bulb within 6 h even though a proinflammatory profile is mounted. Activated microglia may have a role in restricting bacteria to the outer layers of the olfactory bulb.

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“…OECs have also been shown to attenuate stimulated nuclear factor κβ translocation in astrocytes, a key response involved in astrocyte activation/inflammation, along with expression of the proinflammatory cytokine granulocyte macrophage colony-stimulating factor. It is thought that insulin-like growth factor-1 secreted by OECs contributes to this modulation of astrocyte activation 72 .…”

Section: Coadministration Of Neurotrophins During Oec Transplantationmentioning

confidence: 99%

Enhancing the Therapeutic Potential of Olfactory Ensheathing Cells in Spinal Cord Repair Using Neurotrophins

et al. 2018

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Autologous olfactory ensheathing cell (OEC) transplantation is a promising therapy for spinal cord injury; however, the efficacy varies between trials in both animals and humans. The main reason for this variability is that the purity and phenotype of the transplanted cells differs between studies. OECs are susceptible to modulation with neurotrophic factors, and thus, neurotrophins can be used to manipulate the transplanted cells into an optimal, consistent phenotype. OEC transplantation can be divided into 3 phases: (1) cell preparation, (2) cell administration, and (3) continuous support to the transplanted cells in situ. The ideal behaviour of OECs differs between these 3 phases; in the cell preparation phase, rapid cell expansion is desirable to decrease the time between damage and transplantation. In the cell administration phase, OEC survival and integration at the injury site, in particular migration into the glial scar, are the most critical factors, along with OEC-mediated phagocytosis of cellular debris. Finally, continuous support needs to be provided to the transplantation site to promote survival of both transplanted cells and endogenous cells within injury site and to promote long-term integration of the transplanted cells and angiogenesis. In this review, we define the 3 phases of OEC transplantation into the injured spinal cord and the optimal cell behaviors required for each phase. Optimising functional outcomes of OEC transplantation can be achieved by modulation of cell behaviours with neurotrophins. We identify the key growth factors that exhibit the strongest potential for optimizing the OEC phenotype required for each phase.

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Olfactory ensheathing cells moderate nuclear factor kappaB translocation in astrocytes

Cited by 12 publications

References 72 publications

Novel factor in olfactory ensheathing cell‐astrocyte crosstalk: Anti‐inflammatory protein α‐crystallin B

Novel factor in olfactory ensheathing cell‐astrocyte crosstalk: Anti‐inflammatory protein α‐crystallin B

Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway

Enhancing the Therapeutic Potential of Olfactory Ensheathing Cells in Spinal Cord Repair Using Neurotrophins

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