Induction and regulation of IL-8 and MCAF production in human brain tumor cell lines and brain tumor tissues.
In order to elucidate the role of inflammatory cytokines in the central nervous system, we examined the production of two leukocyte chemoattractants, IL-8 and monocyte chemotactic and activating factor (MCAF) in brain tumor cell lines. The glioma cell lines tested exhibited high levels of IL-8 and MCAF mRNA expression upon stimulation with IL-1 or TNF-alpha, while none of the neuroblastoma cell lines expressed these cytokine mRNA. Both IL-8 and MCAF mRNA expression depended on the dose of IL-1 alpha and TNF-alpha and appeared very rapidly, reaching maximal levels at 3-6 hr, with substantial production of these cytokines in the culture supernatants. When various immunosuppressive drugs were tested, glucocorticoids but not other immunosuppressive drugs markedly inhibited the IL-1 or TNF-alpha-induced IL-8 and MCAF mRNA accumulation, suggesting that glucocorticoid is a potent regulator of these inflammatory cytokine production in the neural tissues. In addition, reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of IL-8 and MCAF mRNA expression in resected brain tumor tissues including glioblastoma, astrocytoma grade 2, ependymoma and medulloblastoma, indicating that these inflammatory cytokines are expressed in vivo.
Morita
M
M
Department of Neurology, Jichi Medical School, Tochigi-ken, Japan.
Kasahara
T
T
Mukaida
N
N
Matsushima
K
K
Nagashima
T
T
Nishizawa
M
M
Yoshida
M
M
D001254:Astrocytoma / Q000276:immunology; D001483:Base Sequence; D001932:Brain Neoplasms / Q000276:immunology*; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D007700:Kinetics; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D005938:Glucocorticoids; D016209:Interleukin-8; D012333:RNA, Messenger