Page 230 - Read Online
P. 230
Figueroa-Hall et al. TLR4-mediated signaling in CHME-5 cells
and mounting data makes clear that microglia have Patient consent
diverse roles in the CNS. It is generally difficult and Not applicable.
expensive to obtain human primary microglia and
experiments are often challenging due to limited Ethics approval
cell numbers. Cell lines are therefore essential to Not applicable.
advance the field of neuroinflammation, in particular,
inflammation exacerbating neurodegenerative
diseases. Relative to other cell types, availability of REFERENCES
microglial cell lines is limited, thus, it is important to
maximize our understanding of those tools that are 1. Kawai T, Akira S. Toll-like receptors and their crosstalk with other
innate receptors in infection and immunity. Immunity 2011;34:637-50.
available. Here, we provide novel insights into CHME-5 2. Takeuchi O, Akira S. Pattern recognition receptors and inflammation.
cells by characterizing TLR4 neuroinflammatory Cell 2010;140:805-20.
signaling, which aligned with responses seen in other 3. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol
microglial cell lines, such as BV2, HAPI, and human 2004;4:499-511.
primary microglia. We have also validated very recent 4. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X,
findings suggesting that subsets of CHME-5 cells, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-
currently in use, are of a rat, not human origin. With Castagnoli P, Layton B, Beutler B. Defective LPS signaling in C3H/
this present research, it is our expectation that CHME-5 HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science
1998;282:2085-8.
will remain a useful tool in the study of microglial cells, 5. Hoebe K, Janssen EM, Kim SO, Alexopoulou L, Flavell RA, Han
particularly as related to neuroinflammation. J, Beutler B. Upregulation of costimulatory molecules induced by
lipopolysaccharide and double-stranded RNA occurs by Trif-dependent
DECLARATIONS 6. and Trif-independent pathways. Nat Immunol 2003;4:1223-9.
Chow JC, Young DW, Golenbock DT, Christ WJ, Gusovsky F.
Toll-like receptor-4 mediates lipopolysaccharide-induced signal
Acknowledgments transduction. J Biol Chem 1999;274:10689-92.
We would like to acknowledge “Cancer Sucks” for 7. Lee CC, Avalos AM, Ploegh HL. Accessory molecules for Toll-like
their contribution to the purchase of the BioRad receptors and their function. Nat Rev Immunol 2012;12:168-79.
Thermocycler. 8. Louveau A, Harris TH, Kipnis J. Revisiting the mechanisms of CNS
OSU-Center for Health Sciences, Department of immune privilege. Trends Immunol 2015;36:569-77.
Pharmacology and Physiology: We would like to thank 9. Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells
Daniel Buck-Clay, Kelly McCracken, and Joni Finfrock are highly dynamic surveillants of brain parenchyma in vivo. Science
2005;308:1314-8.
for technical assistance with this project. 10. Graeber MB, Streit WJ. Microglia: biology and pathology. Acta
OSU Center for Health Sciences, Department of Neuropathol 2010;119:89-105.
Forensics: We would like to thank Jun Fu, Ph.D. 11. Rock RB, Gekker G, Hu S, Sheng WS, Cheeran M, Lokensgard JR,
and Robert Allen, Ph.D. for performing the STR Peterson PK. Role of microglia in central nervous system infections.
genotyping on CHME-5 sample. Clin Microbiol Rev 2004;17:942-64.
12. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms
underlying inflammation in neurodegeneration. Cell 2010;140:918-34.
Authors’ contributions 13. Diestel A, Aktas O, Hackel D, Hake I, Meier S, Raine CS,
Concept, design, literature search, experimental Nitsch R, Zipp F, Ullrich O. Activation of microglial poly(ADP-
studies, data acquisition, data analysis, statistical ribose)-polymerase-1 by cholesterol breakdown products during
analysis, manuscript preparation, and manuscript neuroinflammation: a link between demyelination and neuronal
editing: L. Figueroa-Hall damage. J Exp Med 2003;198:1729-40.
Data acquisition and data analysis for fluorescence 14. Aktas O, Ullrich O, Infante-Duarte C, Nitsch R, Zipp F. Neuronal
studies, manuscript review: M. Anderson damage in brain inflammation. Arch Neurol 2007;64:185-9.
Design, data analysis, manuscript editing: S. Das 15. Akiyama H, Arai T, Kondo H, Tanno E, Haga C, Ikeda K. Cell
Experimental design, manuscript editing, manuscript mediators of inflammation in the Alzheimer disease brain. Alzheimer
Dis Assoc Disord 2000;14 Suppl 1:S47-53.
review: C.W. Stevens 16. Gao HM, Liu B, Zhang W, Hong JS. Novel anti-inflammatory therapy
Concept, definition of intellectual content, manuscript for Parkinson’s disease. Trends Pharmacol Sci 2003;24:395-401.
editing and review: R.L. Davis 17. Bsibsi M, Ravid R, Gveric D, van Noort JM. Broad expression of Toll-
like receptors in the human central nervous system. J Neuropathol
Financial support and sponsorship Exp Neurol 2002;61:1013-21.
Oklahoma Center for the Advancement of Science & 18. Laflamme N, Rivest S. Toll-like receptor 4: the missing link of the
cerebral innate immune response triggered by circulating gram-
Technology-HR14-007. negative bacterial cell wall components. FASEB J 2001;15:155-63.
19. Janabi N, Peudenier S, Héron B, Ng KH, Tardieu M. Establishment
Conflicts of interest of human microglial cell lines after transfection of primary cultures of
There are no conflicts of interest. embryonic microglial cells with the SV40 large T antigen. Neurosci
230 Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ October 19, 2017