PMID- 20351184
OWN - NLM
STAT- MEDLINE
DCOM- 20100701
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 184
IP  - 9
DP  - 2010 May 1
TI  - IL-17 enhancement of the IL-6 signaling cascade in astrocytes.
PG  - 4898-906
LID - 10.4049/jimmunol.1000142 [doi]
AB  - Astrocytes have important physiological roles in CNS homeostasis and serve as a 
      bridge between the CNS and immune system. IL-17 and IL-6 are important in many 
      CNS disorders characterized by neuroinflammation. We examined the role of IL-17 
      on the IL-6 signaling cascade in primary astrocytes. IL-17 functioned in a 
      synergistic manner with IL-6 to induce IL-6 expression in astrocytes. The 
      synergistic effect involved numerous signaling pathways including NF-kappaB, JNK 
      MAPK, and p38 MAPK. The NF-kappaB pathway inhibitor BAY-11, JNK inhibitor JNKi 
      II, and p38 inhibitor SB203580 suppressed the synergistic effect of IL-6 and 
      IL-17 on IL-6 expression. IL-17 synergized with IL-6 to enhance the recruitment 
      of activated NF-kappaB p65, c-Fos, c-Jun, and the histone acetyltransferases 
      CREB-binding protein and p300 to the IL-6 promoter in vivo to induce IL-6 
      transcription. This was accompanied by enhanced acetylation of histones H3 and H4 
      on the IL-6 promoter. Moreover, we elucidated an important role for suppressor of 
      cytokine signaling (SOCS) 3 in IL-17 enhancement of IL-6 signaling in astrocytes. 
      SOCS3 small interfering RNA knockdown and SOCS3 deletion in astrocytes augmented 
      the synergistic effect of IL-6 and IL-17 due to an enhancement of activation of 
      the NF-kappaB and MAPK pathways. These results indicate that astrocytes can serve 
      as a target of Th17 cells and IL-17 in the CNS, and SOCS3 participates in IL-17 
      functions in the CNS as a negative feedback regulator.
FAU - Ma, Xiangyu
AU  - Ma X
AD  - Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 
      35294, USA.
FAU - Reynolds, Stephanie L
AU  - Reynolds SL
FAU - Baker, Brandi J
AU  - Baker BJ
FAU - Li, Xingang
AU  - Li X
FAU - Benveniste, Etty N
AU  - Benveniste EN
FAU - Qin, Hongwei
AU  - Qin H
LA  - eng
GR  - R01 NS050665/NS/NINDS NIH HHS/United States
GR  - T32 NS048039/NS/NINDS NIH HHS/United States
GR  - P30 AR048311/AR/NIAMS NIH HHS/United States
GR  - CA1059-A-13/CA/NCI NIH HHS/United States
GR  - R01 NS057563/NS/NINDS NIH HHS/United States
GR  - NS-57563/NS/NINDS NIH HHS/United States
GR  - NS-50665/NS/NINDS NIH HHS/United States
GR  - T32-NS-48039/NS/NINDS NIH HHS/United States
GR  - AR-48311/AR/NIAMS NIH HHS/United States
GR  - NS-50665-05WI/NS/NINDS NIH HHS/United States
GR  - RG 3892-A-12/RG/CSR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100329
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Il17a protein, mouse)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
SB  - IM
MH  - Animals
MH  - Astrocytes/*immunology/*metabolism
MH  - Cells, Cultured
MH  - Gene Expression Regulation/immunology
MH  - Humans
MH  - Interleukin-17/*physiology
MH  - Interleukin-6/biosynthesis/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Receptors, Interleukin-6/physiology
MH  - Recombinant Proteins/pharmacology
MH  - Signal Transduction/genetics/*immunology
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins/deficiency/genetics/physiology
MH  - Up-Regulation/genetics/*immunology
PMC - PMC3769161
MID - NIHMS374367
EDAT- 2010/03/31 06:00
MHDA- 2010/07/02 06:00
PMCR- 2013/09/10
CRDT- 2010/03/31 06:00
PHST- 2010/03/31 06:00 [entrez]
PHST- 2010/03/31 06:00 [pubmed]
PHST- 2010/07/02 06:00 [medline]
PHST- 2013/09/10 00:00 [pmc-release]
AID - jimmunol.1000142 [pii]
AID - 10.4049/jimmunol.1000142 [doi]
PST - ppublish
SO  - J Immunol. 2010 May 1;184(9):4898-906. doi: 10.4049/jimmunol.1000142. Epub 2010 
      Mar 29.