Enteric glia: A new player in inflammatory bowel diseases

Capoccia, Elena; Cirillo, Carla; Gigli, Silvia; Pesce, Marcella; D’Alessandro, Alessandra; Cuomo, Rosario; Sarnelli, Giovanni; Steardo, Luca; Esposito, Giuseppe

doi:10.1177/0394632015599707

Cited by 45 publications

(34 citation statements)

References 69 publications

(104 reference statements)

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“…Thus, enteroglial S100B protein, when over‐expressed and released, is regarded as a pivotal participant in the cascade of events able to induce chronic inflammatory changes in gut mucosa (Capoccia et al . ; Ochoa‐Cortes et al . ).…”

Section: S100b As An Active Factor In Neural Injurymentioning

confidence: 98%

The S100B story: from biomarker to active factor in neural injury

Michetti

D’Ambrosi

Toesca

et al. 2018

Journal of Neurochemistry

263

238

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S100B is a Ca -binding protein mainly concentrated in astrocytes. Its levels in biological fluids (cerebrospinal fluid, peripheral and cord blood, urine, saliva, amniotic fluid) are recognized as a reliable biomarker of active neural distress. Although the wide spectrum of diseases in which the protein is involved (acute brain injury, neurodegenerative diseases, congenital/perinatal disorders, psychiatric disorders) reduces its specificity, its levels remain an important aid in monitoring the trend of the disorder. Mounting evidence now points to S100B as a Damage-Associated Molecular Pattern molecule which, when released at high concentration, through its Receptor for Advanced Glycation Endproducts, triggers tissue reaction to damage in a series of different neural disorders. This review addresses this novel scenario, presenting data indicating that S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease: acute brain injury (ischemic/hemorrhagic stroke, traumatic injury), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis), congenital/perinatal disorders (Down syndrome, spinocerebellar ataxia-1), psychiatric disorders (schizophrenia, mood disorders), inflammatory bowel disease. In many cases, over-expression/administration of the protein induces worsening of the disease, whereas its deletion/inactivation produces amelioration. This review points out that the pivotal role of the protein resulting from these data, opens the perspective that S100B may be regarded as a therapeutic target for these different diseases, which appear to share some common features reasonably attributable to neuroinflammation, regardless their origin.

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Section: S100b As An Active Factor In Neural Injurymentioning

confidence: 98%

The S100B story: from biomarker to active factor in neural injury

Michetti

D’Ambrosi

Toesca

et al. 2018

Journal of Neurochemistry

263

238

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“…As mentioned, EGCs are activated in UC patients as shown by an increased S100b, GDNF, and GFAP expression but there is also an increased NO production through stimulation of iNOS via the RAGE pathway (Capoccia et al, ; Cirillo et al, , ; Esposito et al, ; von Boyen et al, ). An interaction of mucosal EGCs with type 3 innate lymphoid cells (ILC3) was recently demonstrated (Ibiza et al, ).…”

Section: Introductionmentioning

confidence: 98%

“…Prominent proinflammatory signaling pathways in EGCs are via TLR3, 4, and 7 (Barajon et al, ; Rosenbaum et al, ). TLR dependent S100b‐RAGE‐pathway drives the iNOS expression and in turns triggers NO release (Capoccia et al, ; Ochoa‐Cortes et al, ; Turco et al, ).…”

Section: Introductionmentioning

confidence: 99%

Enteric Glia: S100, GFAP, and Beyond

Grundmann

Loris

Maas-Omlor

et al. 2019

The Anatomical Record

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Since several years, the enteric nervous system (ENS) is getting more and more in the focus of gastrointestinal research. While the main interest was credited for years to the enteric neurons and their functional properties, less attention has been paid on the enteric glial cells (EGCs). Although the similarity of EGCs to central nervous system (CNS) astrocytes has been demonstrated a long time ago, EGCs were investigated in more detail only recently. Similar to the CNS, there is not "the" EGC, but also a broad range of diversity. Based on morphology and protein expression, such as glial fibrillary acidic protein (GFAP), S100, or Proteolipid-protein-1 (PLP1), several distinct glial types can be differentiated. Their heterogeneity in morphology, localization, and transcription as well as interaction with surrounding cells indicate versatile functional properties of these cells for gut function in health and disease. Although NG2 is found in a subset of CNS glial cells, it did not colocalize with the glial marker S100 or GFAP in the ENS. Instead, it in part colocalize with PDGFRα, as it does in the CNS, which do stain fibroblast-like cells in the gastrointestinal tract. Moreover, there seem to be species dependent differences. While GFAP is always found in the rodent ENS, this is completely different for the human gut.Only the compromised human ENS shows a significant amount of GFAPpositive glial cells. So, in general we can conclude that the EGC population is species specific and as complex as CNS glia. Anat Rec, 302:1333Rec, 302: -1344Rec, 302: , 2019.

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“…The neural crest marker Sox10 is the most widely expressed in ECGs, although none of the three markers exhibit a pan-expression in EGCs [17]. The EGCs, like all glial cells, are highly active and may undergo plastic changes in response to harmful stimuli, for example during an inflammatory injury, characterized by "reactive gliosis" associated to overexpression of GFAP or S100β [2,18,19].Derangement of the ENS architecture during gut neuropathies may underlie development of functional bowel disorders, often exhibiting an unbalanced equilibrium between excitatory and inhibitory neurotransmission. A dysregulated neurotransmission affects enteric reflexes which are finely tuned by the cross signaling between enteric neurons and glia.…”

mentioning

confidence: 99%

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confidence: 99%

Involvement of Enteric Glia in Small Intestine Neuromuscular Dysfunction of Toll-Like Receptor 4-Deficient Mice

Cerantola

Caputi

Marsilio

et al. 2020

Cells

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Enteric glial cells (EGCs) influence nitric oxide (NO)− and adenosine diphosphate (ADP)− mediated signaling in the enteric nervous system (ENS). Since Toll-like receptor 4 (TLR4) participates to EGC homoeostasis, this study aimed to evaluate the possible involvement of EGCs in the alterations of the inhibitory neurotransmission in TLR4−/− mice. Ileal segments from male TLR4−/− and wild-type (WT) C57BL/6J mice were incubated with the gliotoxin fluoroacetate (FA). Alterations in ENS morphology and neurochemical coding were investigated by immunohistochemistry whereas neuromuscular responses were determined by recording non-adrenergic non-cholinergic (NANC) relaxations in isometrically suspended isolated ileal preparations. TLR4−/− ileal segments showed increased iNOS immunoreactivity associated with enhanced NANC relaxation, mediated by iNOS-derived NO and sensitive to P2Y1 inhibition. Treatment with FA diminished iNOS immunoreactivity and partially abolished NO− and ADP− mediated relaxation in the TLR4−/− mouse ileum, with no changes of P2Y1 and connexin-43 immunofluorescence distribution in the ENS. After FA treatment, S100β and GFAP immunoreactivity in TLR4−/− myenteric plexus was reduced to levels comparable to those observed in WT. Our findings show the involvement of EGCs in the alterations of ENS architecture and in the increased purinergic and nitrergic-mediated relaxation, determining gut dysmotility in TLR4−/− mice.

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Enteric glia: A new player in inflammatory bowel diseases

Cited by 45 publications

References 69 publications

The S100B story: from biomarker to active factor in neural injury

The S100B story: from biomarker to active factor in neural injury

Enteric Glia: S100, GFAP, and Beyond

Involvement of Enteric Glia in Small Intestine Neuromuscular Dysfunction of Toll-Like Receptor 4-Deficient Mice

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