Human astrocyte growth regulation: interleukin-4 sensitivity and receptor expression.
We previously reported that interleukin-4 (IL-4) inhibited proliferation of a human astrocytic cell line derived from non-neoplastic adult cortex. To determine whether this effect was receptor-associated and/or limited to only non-neoplastic astrocytes, we examined IL-4 responsiveness and receptor expression in human astrocytic cell lines derived from three different sources: non-neoplastic cerebral cortex (lines P1N, P2N, W3N); neoplastic low grade astrocytoma (LGA) (lines FRLGA, RTLGA); and highly malignant glioblastoma multiforme (GBM) (lines STTG1, CRTG2, WITG3, RUTG4). All lines except RUTG4 GBM expressed IL-4 receptor mRNA. Proliferation and DNA synthesis were markedly suppressed by IL-4 in a dose- and time-dependent manner in all non-neoplastic astrocyte and LGA lines, but not (0/4) GBM. This negative growth-regulatory effect of IL-4 was blocked by specific antibody to human IL-4 receptor but not by irrelevant IgG. In contrast, IL-4 stimulated interleukin-6 (IL-6) secretion in non-neoplastic astrocytes and LGA as well as in GBM cells expressing IL-4 receptor; secretion was undetectable in RUTG4 GBM which did not express receptor. These results indicate that: (i) responsiveness to IL-4 occurs in both non-neoplastic and neoplastic human astroglia; (ii) responsiveness is associated with IL-4 receptor expression; and (iii) sensitivity to negative growth signalling by IL-4 occurs selectively in astrocytes from non-neoplastic cortex or low grade neoplasia but not from highly malignant GBM.
Barna
B P
BP
Department of Clinical Pathology, Cleveland Clinic Foundation, OH 44195-5131, USA.
Estes
M L
ML
Pettay
J
J
Iwasaki
K
K
Zhou
P
P
Barnett
G H
GH
D001253:Astrocytes / Q000166:cytology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D013997:Time Factors
D015850:Interleukin-6; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D015847:Interleukin-4