TY - JOUR
T1 - Tetraethylammonium, a K+ channel blocker, inhibits interferon-γ-induced major histocompatibility class II antigen (Ia) expression and DNA synthesis in rat astrocytes
AU - Ohira, Kiyoshi
AU - Vayuvegula, Bharathi
AU - Murakami, Masaru
AU - Gollapudi, Sastry
AU - Frohman, Elliot
AU - van den Noort, Stanley
AU - Gupta, Sudhir
PY - 1991/1
Y1 - 1991/1
N2 - Astrocytes play an important role in antigen presentation to T lymphocytes by their ability to express major histocompatibility class II (Ia) antigen upon exposure to a number of agents, including interferon-γ (IFN-γ). Astrocytes have been shown to express a variety of voltage-sensitive ion channels including voltage-sensitive K+ channels. The function(s) of these channels in astrocyte functions is not clearly understood. In this investigation, we examined: (1) the comparative effects of mouse, rat, and human recombinant IFN-γ (rIFN-γ) on the induction of Ia antigen and DNA synthesis in rat astrocytes; (2) the effect of tetraethylammonium (TEA), a K+ channel blocker, on rat IFN-γ-induced Ia expression and DNA synthesis in rat astrocytes. Our data show that all INF-γ induce DNA synthesis in rat astrocytes but only rat and mouse and not the human IFN-γ will induce Ia expression. TEA in a dose-dependent manner inhibited both Ia expression and DNA synthesis in rat astrocytes. The concentration kinetics of TEA with regard to maximum inhibition of Ia and DNA synthesis were different. Furthermore, these inhibitory effects were not a result of toxic or nonspecific effect of TEA on astrocytes as demonstrated by viability data and lack of any effect of tetramethylammonium, an analogue of TEA, that does not block K+ ion channels. These data suggest a role of K+ channels in Ia expression and DNA synthesis, therefore in immunological functions of astrocytes.
AB - Astrocytes play an important role in antigen presentation to T lymphocytes by their ability to express major histocompatibility class II (Ia) antigen upon exposure to a number of agents, including interferon-γ (IFN-γ). Astrocytes have been shown to express a variety of voltage-sensitive ion channels including voltage-sensitive K+ channels. The function(s) of these channels in astrocyte functions is not clearly understood. In this investigation, we examined: (1) the comparative effects of mouse, rat, and human recombinant IFN-γ (rIFN-γ) on the induction of Ia antigen and DNA synthesis in rat astrocytes; (2) the effect of tetraethylammonium (TEA), a K+ channel blocker, on rat IFN-γ-induced Ia expression and DNA synthesis in rat astrocytes. Our data show that all INF-γ induce DNA synthesis in rat astrocytes but only rat and mouse and not the human IFN-γ will induce Ia expression. TEA in a dose-dependent manner inhibited both Ia expression and DNA synthesis in rat astrocytes. The concentration kinetics of TEA with regard to maximum inhibition of Ia and DNA synthesis were different. Furthermore, these inhibitory effects were not a result of toxic or nonspecific effect of TEA on astrocytes as demonstrated by viability data and lack of any effect of tetramethylammonium, an analogue of TEA, that does not block K+ ion channels. These data suggest a role of K+ channels in Ia expression and DNA synthesis, therefore in immunological functions of astrocytes.
KW - Astrocyte
KW - DNA synthesis
KW - Ia antigen
KW - Interferon-γ
KW - Potassium channel
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U2 - 10.1016/0165-5728(91)90085-L
DO - 10.1016/0165-5728(91)90085-L
M3 - Article
C2 - 1898518
AN - SCOPUS:0026013340
SN - 0165-5728
VL - 31
SP - 43
EP - 49
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1
ER -