Abstract
Interleukin (IL)-6 expression transiently increases in the acute phase of cerebral ischemia. To investigate the physiological significance of endogenous IL-6 expression and to identify the main signal pathway for the action of IL-6, we administered anti-mouse IL-6 receptor monoclonal antibody (IL-6RA), which blocks IL-6 signaling, to mice immediately after a 45-min period of middle cerebral artery occlusion (MCAO). At 6 h after MCAO, IL-6RA administration had resulted in a significant reduction in the amount of phosphorylated signal transducer and activator of transcription-3 (Stat3) protein in the peri-infarct area of the cortex. At 24 h after MCAO, blockade of IL-6 signaling had led to an increase in number of apoptotic cells in the peri-infarct area and enlargement of the size of the infarct, and it had adversely affected neurological function. These results suggest that endogenous IL-6 plays a critical role in preventing damaged neurons from undergoing apoptosis in the acute phase of cerebral ischemia and that its role may be mediated by Stat3 activation.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antibodies, Monoclonal / pharmacology
-
Apoptosis / drug effects
-
Behavior, Animal
-
Blotting, Western / methods
-
Brain Ischemia / etiology
-
Brain Ischemia / metabolism*
-
Brain Ischemia / pathology
-
Caspase 3
-
Caspases / metabolism
-
Cell Count / methods
-
Cerebral Cortex / cytology*
-
Cerebral Cortex / pathology
-
Chi-Square Distribution
-
DNA-Binding Proteins / metabolism*
-
Enzyme Activation / drug effects
-
Enzyme-Linked Immunosorbent Assay / methods
-
Extracellular Signal-Regulated MAP Kinases / metabolism
-
Histocytochemistry / methods
-
Infarction, Middle Cerebral Artery / complications
-
Interleukin-6 / antagonists & inhibitors*
-
Interleukin-6 / metabolism
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Neurons / drug effects*
-
Phosphorylation / drug effects
-
Protein Serine-Threonine Kinases / metabolism
-
Proto-Oncogene Proteins / metabolism
-
Proto-Oncogene Proteins c-akt
-
RNA, Messenger / metabolism
-
Receptors, Interleukin-6 / antagonists & inhibitors
-
Receptors, Interleukin-6 / immunology
-
Repressor Proteins / genetics
-
Repressor Proteins / metabolism
-
Reverse Transcriptase Polymerase Chain Reaction / methods
-
STAT3 Transcription Factor
-
Signal Transduction / drug effects
-
Suppressor of Cytokine Signaling 3 Protein
-
Suppressor of Cytokine Signaling Proteins
-
Time Factors
-
Trans-Activators / metabolism*
-
Transcription Factors / genetics
-
Transcription Factors / metabolism
Substances
-
Antibodies, Monoclonal
-
DNA-Binding Proteins
-
Interleukin-6
-
Proto-Oncogene Proteins
-
RNA, Messenger
-
Receptors, Interleukin-6
-
Repressor Proteins
-
STAT3 Transcription Factor
-
Socs3 protein, mouse
-
Stat3 protein, mouse
-
Suppressor of Cytokine Signaling 3 Protein
-
Suppressor of Cytokine Signaling Proteins
-
Trans-Activators
-
Transcription Factors
-
Protein Serine-Threonine Kinases
-
Proto-Oncogene Proteins c-akt
-
Extracellular Signal-Regulated MAP Kinases
-
Casp3 protein, mouse
-
Caspase 3
-
Caspases