Limits...
Downregulation of CD47 and CD200 in patients with focal cortical dysplasia type IIb and tuberous sclerosis complex.

Sun FJ, Zhang CQ, Chen X, Wei YJ, Li S, Liu SY, Zang ZL, He JJ, Guo W, Yang H - J Neuroinflammation (2016)

Bottom Line: We investigate the levels and expression pattern of CD47/SIRP-α and CD200/CD200R in surgically resected brain tissues from patients with FCD IIb and TSC, and the potential effect of soluble human CD47 Fc and CD200 Fc on the inhibition of several proinflammatory cytokines associated with FCD IIb and TSC in living epileptogenic brain slices in vitro.Both the messenger RNA and protein levels of CD47, SIRP-α, and CD200, as well as the mRNA level of IL-4, were downregulated in epileptogenic lesions of FCD IIb and TSC compared with the control specimens, whereas CD200R levels were not significantly changed.CD47 Fc and CD200 Fc could inhibit IL-6 release but did not suppress IL-1β or IL-17 production.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, 2-V Xinqiao Street, Chongqing, 400037, China.

ABSTRACT

Background: Focal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are well-recognized causes of chronic intractable epilepsy in children. Accumulating evidence suggests that activation of the microglia/macrophage and concomitant inflammatory response in FCD IIb and TSC may contribute to the initiation and recurrence of seizures. The membrane glycoproteins CD47 and CD200, which are highly expressed in neurons and other cells, mediate inhibitory signals through their receptors, signal regulatory protein α (SIRP-α) and CD200R, respectively, in microglia/macrophages. We investigate the levels and expression pattern of CD47/SIRP-α and CD200/CD200R in surgically resected brain tissues from patients with FCD IIb and TSC, and the potential effect of soluble human CD47 Fc and CD200 Fc on the inhibition of several proinflammatory cytokines associated with FCD IIb and TSC in living epileptogenic brain slices in vitro. The level of interleukin-4 (IL-4), a modulator of CD200, was also investigated.

Methods: Twelve FCD IIb (range 1.8-9.5 years), 13 TSC (range 1.5-10 years) patients, and 6 control cases (range 1.5-11 years) were enrolled. The levels of CD47/SIRP-α and CD200/CD200R were assessed by quantitative real-time polymerase chain reaction and western blot. The expression pattern of CD47/SIRP-α and CD200/CD200R was investigated by immunohistochemical analysis, and the cytokine concentrations were measured by enzyme-linked immune-sorbent assays.

Results: Both the messenger RNA and protein levels of CD47, SIRP-α, and CD200, as well as the mRNA level of IL-4, were downregulated in epileptogenic lesions of FCD IIb and TSC compared with the control specimens, whereas CD200R levels were not significantly changed. CD47, SIRP-α, and CD200 were decreasingly expressed in dysmorphic neuron, balloon cells, and giant cells. CD47 Fc and CD200 Fc could inhibit IL-6 release but did not suppress IL-1β or IL-17 production.

Conclusions: Our results suggest that microglial activation may be partially caused by CD47/SIRP-α- and CD200/CD200R-mediated reductions in the immune inhibitory pathways within FCD IIb and TSC cortical lesions where chronic neuroinflammation has been established. Upregulation or activation of CD47/SIRP-α and CD200/CD200R may have therapeutic potential for controlling neuroinflammation in human FCD IIb and TSC.

No MeSH data available.


Related in: MedlinePlus

Effects of soluble recombinant human CD47 Fc Chimera protein and CD200 Fc chimera protein on the production of IL-1β, IL-6, and IL-17, as measured by ELISAs. IL-1β release was not inhibited by CD47 Fc (a) or CD200 Fc (b). Both CD47 Fc (c) and CD200 Fc (d) reduced the IL-6 production. The IL-17 release was not suppressed by CD47 Fc (e) or CD200 Fc (f). These data are representative of four experiments. The bar charts represent mean ± SD, Mann–Whitney U test, *P < 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4837553&req=5

Fig9: Effects of soluble recombinant human CD47 Fc Chimera protein and CD200 Fc chimera protein on the production of IL-1β, IL-6, and IL-17, as measured by ELISAs. IL-1β release was not inhibited by CD47 Fc (a) or CD200 Fc (b). Both CD47 Fc (c) and CD200 Fc (d) reduced the IL-6 production. The IL-17 release was not suppressed by CD47 Fc (e) or CD200 Fc (f). These data are representative of four experiments. The bar charts represent mean ± SD, Mann–Whitney U test, *P < 0.05

Mentions: The concentration of cytokines was measured by ELISAs. Both CD47 Fc and CD200 Fc could reduce the IL-6 production (P < 0.05; Fig. 9c, d). Interestingly, IL-1β and IL-17 that were closely associated with IL-6 in epileptogenic lesions of MCD were not suppressed by CD47 Fc (P > 0.05; Fig. 9a, b) or CD200 Fc (P > 0.05; Fig. 9e, f).Fig. 9


Downregulation of CD47 and CD200 in patients with focal cortical dysplasia type IIb and tuberous sclerosis complex.

Sun FJ, Zhang CQ, Chen X, Wei YJ, Li S, Liu SY, Zang ZL, He JJ, Guo W, Yang H - J Neuroinflammation (2016)

Effects of soluble recombinant human CD47 Fc Chimera protein and CD200 Fc chimera protein on the production of IL-1β, IL-6, and IL-17, as measured by ELISAs. IL-1β release was not inhibited by CD47 Fc (a) or CD200 Fc (b). Both CD47 Fc (c) and CD200 Fc (d) reduced the IL-6 production. The IL-17 release was not suppressed by CD47 Fc (e) or CD200 Fc (f). These data are representative of four experiments. The bar charts represent mean ± SD, Mann–Whitney U test, *P < 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4837553&req=5

Fig9: Effects of soluble recombinant human CD47 Fc Chimera protein and CD200 Fc chimera protein on the production of IL-1β, IL-6, and IL-17, as measured by ELISAs. IL-1β release was not inhibited by CD47 Fc (a) or CD200 Fc (b). Both CD47 Fc (c) and CD200 Fc (d) reduced the IL-6 production. The IL-17 release was not suppressed by CD47 Fc (e) or CD200 Fc (f). These data are representative of four experiments. The bar charts represent mean ± SD, Mann–Whitney U test, *P < 0.05
Mentions: The concentration of cytokines was measured by ELISAs. Both CD47 Fc and CD200 Fc could reduce the IL-6 production (P < 0.05; Fig. 9c, d). Interestingly, IL-1β and IL-17 that were closely associated with IL-6 in epileptogenic lesions of MCD were not suppressed by CD47 Fc (P > 0.05; Fig. 9a, b) or CD200 Fc (P > 0.05; Fig. 9e, f).Fig. 9

Bottom Line: We investigate the levels and expression pattern of CD47/SIRP-α and CD200/CD200R in surgically resected brain tissues from patients with FCD IIb and TSC, and the potential effect of soluble human CD47 Fc and CD200 Fc on the inhibition of several proinflammatory cytokines associated with FCD IIb and TSC in living epileptogenic brain slices in vitro.Both the messenger RNA and protein levels of CD47, SIRP-α, and CD200, as well as the mRNA level of IL-4, were downregulated in epileptogenic lesions of FCD IIb and TSC compared with the control specimens, whereas CD200R levels were not significantly changed.CD47 Fc and CD200 Fc could inhibit IL-6 release but did not suppress IL-1β or IL-17 production.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, 2-V Xinqiao Street, Chongqing, 400037, China.

ABSTRACT

Background: Focal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are well-recognized causes of chronic intractable epilepsy in children. Accumulating evidence suggests that activation of the microglia/macrophage and concomitant inflammatory response in FCD IIb and TSC may contribute to the initiation and recurrence of seizures. The membrane glycoproteins CD47 and CD200, which are highly expressed in neurons and other cells, mediate inhibitory signals through their receptors, signal regulatory protein α (SIRP-α) and CD200R, respectively, in microglia/macrophages. We investigate the levels and expression pattern of CD47/SIRP-α and CD200/CD200R in surgically resected brain tissues from patients with FCD IIb and TSC, and the potential effect of soluble human CD47 Fc and CD200 Fc on the inhibition of several proinflammatory cytokines associated with FCD IIb and TSC in living epileptogenic brain slices in vitro. The level of interleukin-4 (IL-4), a modulator of CD200, was also investigated.

Methods: Twelve FCD IIb (range 1.8-9.5 years), 13 TSC (range 1.5-10 years) patients, and 6 control cases (range 1.5-11 years) were enrolled. The levels of CD47/SIRP-α and CD200/CD200R were assessed by quantitative real-time polymerase chain reaction and western blot. The expression pattern of CD47/SIRP-α and CD200/CD200R was investigated by immunohistochemical analysis, and the cytokine concentrations were measured by enzyme-linked immune-sorbent assays.

Results: Both the messenger RNA and protein levels of CD47, SIRP-α, and CD200, as well as the mRNA level of IL-4, were downregulated in epileptogenic lesions of FCD IIb and TSC compared with the control specimens, whereas CD200R levels were not significantly changed. CD47, SIRP-α, and CD200 were decreasingly expressed in dysmorphic neuron, balloon cells, and giant cells. CD47 Fc and CD200 Fc could inhibit IL-6 release but did not suppress IL-1β or IL-17 production.

Conclusions: Our results suggest that microglial activation may be partially caused by CD47/SIRP-α- and CD200/CD200R-mediated reductions in the immune inhibitory pathways within FCD IIb and TSC cortical lesions where chronic neuroinflammation has been established. Upregulation or activation of CD47/SIRP-α and CD200/CD200R may have therapeutic potential for controlling neuroinflammation in human FCD IIb and TSC.

No MeSH data available.


Related in: MedlinePlus