The regulation of reactive changes around multiple sclerosis lesions by phosphorylated signal transducer and activator of transcription.
Activation of signal transducer and activator of transcription 3 (STAT3) by phosphorylation is thought to mediate anti-inflammatory responses to CNS injury. Several studies have reported an increase in phosphorylated STAT3 (pSTAT3) in peripheral T cells and monocytes from patients with multiple sclerosis (MS) during relapses, suggesting that pSTAT3 might represent an inflammatory marker. Here, we examined immunoreactivity for pSTAT3 in brain tissue samples from MS patients and controls. Phosphorylated STAT3 immunoreactivity was sparse within lesions, with no difference between active and inactive lesions. It was, however, significantly greater in white matter (WM) adjacent to active and inactive lesions; moreover, it was significantly greater in WM adjacent to active versus inactive lesions. Phosphorylated STAT3-positive cells were identified as astrocytes and macrophages/microglia. Phosphorylated STAT3 expression was also detected by Western blotting in WM of patients with MS. In comparison, pSTAT3 immunoreactivity was either rare or found focally in brain tissue samples from patients with other neurologic diseases. Our findings show that pSTAT3 does not correlate with inflammatory activity in MS lesions, but that it may play an important role in regulating reactive changes proximal to MS lesions.
From the Departments of Laboratory Medicine and Pathology (JQL), and Medicine/Neurology (CP, GB, FG), University of Alberta, Edmonton, Alberta, Canada; and Departments of Clinical Neurosciences and Oncology, University of Calgary, Calgary, Alberta, Canada (VWY).
Jian-Qiang
JQ
Lu
Christopher
C
Power
Gregg
G
Blevins
Fabrizio
F
Giuliani
V Wee
VW
Yong
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011180:Postmortem Changes; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D055815:Young Adult; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D050796:STAT3 Transcription Factor; C112986:AIF1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule