The mTOR kinase inhibitor rapamycin enhances the expression and release of pro-inflammatory cytokine interleukin 6 modulating the activation of human microglial cells

Simple item page
dc.contributor.authorCappoli, Natalia
dc.contributor.authorMezzogori, Daniele
dc.contributor.authorTabolacci, Elisabetta
dc.contributor.authorColetta, Isabella
dc.contributor.authorNavarra, Pierluigi
dc.contributor.authorPani, Giovambattista
dc.contributor.authorDello Russo, Cinzia
dc.date.accessioned2020-03-06T13:21:23Z
dc.date.available2020-03-06T13:21:23Z
dc.date.issued2019-09-06
dc.description.abstractEmerging evidence suggests the potential use of rapamycin in treatment of several neurological disorders. The drug readily crosses the blood brain barrier and may exert direct immunomodulatory effects within the brain. Microglia are the main innate immune cells of the brain, thus critically involved in the initiation and development of inflammatory processes at this level. However, there are conflicting data from rodent studies about the pharmacological effects of rapamycin on microglial inflammatory responses. Considering that rodent microglia display relevant biochemical and harmacological differences compared to human microglia, in the present study we studied the effects of rapamycin in an experimental model of human microglia, the human microglial clone 3 (HMC3) cell line. Rapamycin was tested in the nM range both under basal conditions and in cells activated with a pro-nflammatory cytokine cocktail, consisting in a mixture of interferon-γ and interleukin-1β (II). The drug significantly increased II stimulatory effect on interleukin-6 (IL-6) expression and release in the HMC3 cells, while reducing the production of free oxygen radicals (ROS) both under basal conditions and in cells activated with II. Consistently with its known molecular mechanism of action, rapamycin reduced the extent of activation of the so-called ‘mechanistic’ target of rapamycin complex 1 (mTORC1) kinase and the total amount of intracellular proteins. In contrast to rodent cells, rapamycin did not alter human microglial cell viability nor inhibited cell proliferation. Moreover, rapamycin did not exert any significant effect on the morphology of the HMC3 cells. All together these data suggest that the inhibition of mTORC1 in human microglia by rapamycin results in complex immunomodulatory effects, including a significant increase in the expression and release of the pro-inflammatory IL-6.en
dc.identifier.issn1611-2156
dc.identifier.urihttp://hdl.handle.net/2003/39048
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-20967
dc.language.isoen
dc.relation.ispartofseriesEXCLI Journal;Vol. 18 2019
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHMC3 microglial cellsen
dc.subjectRapamycinen
dc.subjectIL-6en
dc.subjectROSen
dc.subjectPro-inflammatory cytokinesen
dc.subject.ddc610
dc.titleThe mTOR kinase inhibitor rapamycin enhances the expression and release of pro-inflammatory cytokine interleukin 6 modulating the activation of human microglial cellsen
dc.typeText
dc.type.publicationtypearticle
dcterms.accessRightsopen access
eldorado.dnb.zdberstkatid2132560-1
eldorado.secondarypublicationtrue

Files

Original bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
Dello_Russo_06092019_proof.pdf
Size:
722.79 KB
Format:
Adobe Portable Document Format
Description:
DNB
Download
Thumbnail Image
Name:
Dello_Russo_06092019_supplementary_material.pdf
Size:
28.3 KB
Format:
Adobe Portable Document Format
Description:
DNB
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
4.85 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Original Articles