PMID- 23439211 OWN - NLM STAT- MEDLINE DCOM- 20130701 LR - 20211021 IS - 1471-4159 (Electronic) IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 125 IP - 4 DP - 2013 May TI - Astrocytes inhibit microglial surface expression of dendritic cell-related co-stimulatory molecules through a contact-mediated process. PG - 575-87 LID - 10.1111/jnc.12221 [doi] AB - Murine microglia cultured in isolation were treated sequentially with granulocyte/monocyte colony-stimulating factor (GM-CSF) (5 days) and lipopolysaccharide (LPS) (2 days) to elicit a mature dendritic cell-like (DC-like) phenotype. Examined by flow cytometry microglia thus isolated show high surface expression of CD11c together with the co-stimulatory molecules CD40, CD80, and CD86 that are necessary for T-cell activation. In contrast, microglia co-cultured with astrocytes fail to achieve a mature DC-like phenotype. Contact with the astrocytic environment is necessary for the inhibition. Failure was not because of a more rapid degradation of protein. Bone marrow-derived cells, like microglia, were prevented by astrocytes from attaining a mature DC phenotype. Although GM-CSF pre-treatment substantially increases mRNA of co-stimulatory molecules and major histocompatibility complex (MHC) Class II in isolated microglia, co-cultured microglia await treatment with LPS to up-regulate them. In contrast, western blot and immunocytochemical analysis revealed that it is not a failure of transcription or translation, nor is it a more rapid degradation of mRNA that is responsible for the low surface expression; rather microglia co-cultured with astrocytes produce mRNA and protein but do not traffic the protein onto the cell surface. CI - (c) 2013 International Society for Neurochemistry. FAU - Acevedo, Giselles AU - Acevedo G AD - Rutgers University/Newark, Newark, New Jersey, USA. FAU - Padala, Nischal K AU - Padala NK FAU - Ni, Li AU - Ni L FAU - Jonakait, G M AU - Jonakait GM LA - eng GR - R25 GM060826/GM/NIGMS NIH HHS/United States GR - R25 GM096161/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20130327 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Antigens, Surface) RN - 0 (B7-1 Antigen) RN - 0 (B7-2 Antigen) RN - 0 (CD11c Antigen) RN - 0 (CD40 Antigens) RN - 0 (Cd86 protein, mouse) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (RNA, Messenger) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Animals, Newborn MH - Antigens, Surface/genetics/metabolism MH - Astrocytes/*cytology/physiology MH - B7-1 Antigen/*genetics/metabolism MH - B7-2 Antigen/*genetics/metabolism MH - CD11c Antigen/genetics/metabolism MH - CD40 Antigens/*genetics/metabolism MH - Cell Communication/physiology MH - Cell Differentiation/drug effects/physiology MH - Cells, Cultured MH - Coculture Techniques MH - Dendritic Cells/*cytology/physiology MH - Female MH - Gene Expression/drug effects/physiology MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Histocompatibility Antigens Class II/genetics/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microglia/*cytology/physiology MH - Phenotype MH - RNA, Messenger/metabolism PMC - PMC3637427 MID - NIHMS449585 COIS- The authors have no conflicts of interest to declare. EDAT- 2013/02/27 06:00 MHDA- 2013/07/03 06:00 PMCR- 2014/05/01 CRDT- 2013/02/27 06:00 PHST- 2013/01/20 00:00 [received] PHST- 2013/02/08 00:00 [revised] PHST- 2013/02/08 00:00 [accepted] PHST- 2013/02/27 06:00 [entrez] PHST- 2013/02/27 06:00 [pubmed] PHST- 2013/07/03 06:00 [medline] PHST- 2014/05/01 00:00 [pmc-release] AID - 10.1111/jnc.12221 [doi] PST - ppublish SO - J Neurochem. 2013 May;125(4):575-87. doi: 10.1111/jnc.12221. Epub 2013 Mar 27.