Abstract | BACKGROUND: METHODS: Stat3 specific siRNA oligo and synthetic selective inhibitor ( Stattic) were applied to block the activity of Stat3 in primary astrocytes or rat spinal cord, respectively. LPS was used to induce the expression of proinflammatory genes in all studies. Immunofluorescence staining of cells and slices of spinal cord was performed to monitor Stat3 activation. The impact of Stat3 inhibition on proinflammatory genes expression was determined by cytokine antibody array, enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Mechanical allodynia, as determined by the threshold pressure that could induce hind paw withdrawal after application of standardized von Frey filaments, was used to detect the effects of Stat3 inhibition after pain development with intrathecal LPS injection. RESULTS:
Intrathecal injection of LPS activated Stat3 in reactive spinal astrocytes. Blockade of Stat3 activity attenuated mechanical allodynia significantly and was correlated with a lower number of reactive astrocytes in the spinal dorsal horn. In vitro study demonstrated that Stat3 modulated inflammatory response in primary astrocytes by transcriptional regulation of chemokine expression including Cx3cl1, Cxcl5, Cxcl10 and Ccl20. Similarly, inhibition of Stat3 reversed the expression of these chemokines in the spinal dorsal horn. CONCLUSIONS: Stat3 acted as a transcriptional regulator of reactive astrocytes by modulating chemokine expression. Stat3 regulated inflammatory response in astrocytes and contributed to pain modulation. Blockade of Stat3 represents a new target for pain control.
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Authors | Xiaodong Liu, Yuanyuan Tian, Na Lu, Tony Gin, Christopher H K Cheng, Matthew T V Chan |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 10
Pg. e75804
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 24098399
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chemokines
- Lipopolysaccharides
- RNA, Small Interfering
- STAT3 Transcription Factor
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Topics |
- Animals
- Astrocytes
(metabolism)
- Chemokines
(genetics)
- Gene Expression Regulation
(drug effects, genetics)
- Hyperalgesia
(genetics, pathology)
- Lipopolysaccharides
(pharmacology)
- Male
- Posterior Horn Cells
(pathology)
- RNA Interference
- RNA, Small Interfering
(genetics)
- Rats
- Rats, Sprague-Dawley
- STAT3 Transcription Factor
(deficiency, genetics)
- Transcription, Genetic
(drug effects, genetics)
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