PMID- 2555395
OWN - NLM
STAT- MEDLINE
DCOM- 19900108
LR  - 20200409
IS  - 0165-5728 (Print)
IS  - 1872-8421 (Electronic)
IS  - 0165-5728 (Linking)
VI  - 25
IP  - 2-3
DP  - 1989 Dec
TI  - Tumor necrosis factor-alpha enhances interferon-gamma-mediated class II antigen 
      expression on astrocytes.
PG  - 209-19
AB  - Astrocytes can function as antigen-presenting cells (APC) upon expression of 
      class II antigens, which are induced by interferon-gamma (IFN-gamma). Tumor 
      necrosis factor-alpha (TNF-alpha) can act synergistically with IFN-gamma with 
      respect to class II expression on a variety of cells. As brain cells themselves 
      can secrete TNF-like factors upon stimulation, we examined the effect of 
      TNF-alpha on IFN-gamma-mediated class II induction on astrocytes. TNF-alpha alone 
      had no effect on class II expression, but did synergize with IFN-gamma for 
      enhanced expression of class II antigens. The specificity of TNF-alpha activity 
      was demonstrated by blocking the amplifying effect of TNF-alpha with a polyclonal 
      anti-TNF-alpha antibody. Kinetic analysis of the synergistic effect indicated 
      that optimal TNF-alpha enhancement of class II expression was observed when 
      astrocytes were pretreated with IFN-gamma 12-24 h prior to TNF-alpha addition. A 
      possible mechanism for the synergistic action between IFN-gamma and TNF-alpha may 
      be increased TNF-alpha receptor expression by IFN-gamma. Astrocytes treated with 
      IFN-gamma for 24 h express more TNF-alpha receptors (3900/cell) than do untreated 
      astrocytes (2483/cell), with no significant change in the binding affinity (Kd). 
      These results suggest that the synergistic activity of TNF-alpha requires an 
      inductive signal from IFN-gamma, which in part may be increased TNF-alpha 
      receptor expression. Altogether, our observations indicate that TNF-alpha 
      enhances ongoing class II major histocompatibility complex gene expression in rat 
      astrocytes, which in this system is initially induced by IFN-gamma. TNF-alpha 
      exerts its effect by binding to high affinity TNF-alpha receptors on astrocytes, 
      whose expression is also enhanced by IFN-gamma. These two cytokines work in 
      concert to elevate class II expression on astrocytes, an event which can 
      contribute to initiation and/or perpetuation of intracerebral immune responses.
FAU - Benveniste, E N
AU  - Benveniste EN
AD  - Department of Neurology, University of Alabama, Birmingham 35294.
FAU - Sparacio, S M
AU  - Sparacio SM
FAU - Bethea, J R
AU  - Bethea JR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Astrocytes/*immunology/metabolism
MH  - Histocompatibility Antigens Class II/*immunology
MH  - Interferon-gamma/*pharmacology
MH  - Kinetics
MH  - Receptors, Cell Surface/metabolism
MH  - Receptors, Tumor Necrosis Factor
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
PMC - PMC7119699
EDAT- 1989/12/01 00:00
MHDA- 2000/06/01 09:00
PMCR- 2002/11/11
CRDT- 1989/12/01 00:00
PHST- 1989/12/01 00:00 [pubmed]
PHST- 2000/06/01 09:00 [medline]
PHST- 1989/12/01 00:00 [entrez]
PHST- 2002/11/11 00:00 [pmc-release]
AID - 0165-5728(89)90139-2 [pii]
AID - 10.1016/0165-5728(89)90139-2 [doi]
PST - ppublish
SO  - J Neuroimmunol. 1989 Dec;25(2-3):209-19. doi: 10.1016/0165-5728(89)90139-2.