Interleukin-1beta induces the expression of lipocortin 1 mRNA in cultured rat cortical astrocytes.
Lipocortin 1 (LC1) has been shown to increase in neuronal damage and act as a neuroprotectant and a neurotrophic factor. IL-1beta acts as a mediator of inflammation and has been reported as a potent inducer of various neurotrophic factors including nerve growth factor and fibroblast growth factor. In this study, we investigated the relationship between LC1 and IL-1beta in cultured rat astrocytes. Time-and dose-dependent experiments of IL-1beta on rat cortical astrocytes in culture revealed that the expression of LC1 mRNA was significantly augmented by IL-1beta at 8 h, 10 ng/ml. In addition, IL-1beta evoked an extracellular secretion of LC1 without its cytotoxic effects. The effect of IL-1beta was completely abolished when we treated cells with inhibitor of mitogen-activated protein kinases (MAPKs) (PD98059) (25 microM), phospholipase A(2) inhibitor mepacrine (30 microM) and protein synthesis inhibitor cycloheximide (CHX) (10 microg/ml). This suggests that induction of LC1 by IL-1beta is through a MAPKs and phospholipaseA(2) pathway and requires protein synthesis. These results indicate that IL-1beta released in the central nervous system (CNS) injury can stimulate the transcription of the LC1 gene. Subsequent synthesis and release of LC1 may provide trophic support to neurons and modulate the action of IL-1beta in brain damage.
Miyachi
T
T
Department of Pediatrics, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan. tai.miya@med.nagoya-cu.ac.jp
Asai
K
K
Tsuiki
H
H
Mizuno
H
H
Yamamoto
N
N
Yokoi
T
T
Aoyama
M
M
Togari
H
H
Wada
Y
Y
Miura
Y
Y
Kato
T
T
D000818:Animals; D017305:Annexin A1 / Q000235:genetics*; D000906:Antibodies / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001930:Brain Injuries / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D017305:Annexin A1; D000906:Antibodies; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D018696:Neuroprotective Agents; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003513:Cycloheximide; D011796:Quinacrine