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Published on: December 8, 2017
SIGIRR modulates the inflammatory response in the brain
Melanie B Watson1, Derek A Costello, Dónal G Carney
1Trinity College Institute for Neuroscience, Physiology Department, Trinity College, Dublin 2, Ireland.
Brain, Behavior, and Immunity
|April 17, 2010
Summary
Single Ig-interleukin-1 related receptor (SIGIRR) deficiency exacerbates neuroinflammation. SIGIRR-deficient mice show heightened responses to lipopolysaccharide (LPS), indicating its crucial role in regulating brain inflammation.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Inflammation Research
Background:
- Single Ig-interleukin-1 related receptor (SIGIRR) is an IL-1 receptor family member acting as a negative regulator of inflammation.
- SIGIRR modulates Toll-like receptor 4 (TLR4) and IL-1 responses in peripheral tissues.
- SIGIRR deficiency leads to exaggerated inflammatory responses and more severe experimental inflammatory conditions.
Purpose of the Study:
- To investigate the role of SIGIRR in regulating neuroinflammation.
- To determine if SIGIRR deficiency is associated with inflammatory changes in the brain.
Main Methods:
- Assessed lipopolysaccharide (LPS)-induced inflammatory responses in mixed glia, purified microglia, and astrocytes from SIGIRR-deficient (SIGIRR-/-) and wildtype mice.
- Measured mRNA and protein levels of inflammatory markers (CD40, ICAM, TNF-alpha, IL-6).
- Evaluated microglial activation, cytokine production, and behavioral changes in response to LPS.
Main Results:
- LPS induced greater CD40 and ICAM mRNA expression in mixed glia from SIGIRR-/- mice compared to wildtype.
- Increased TNF-alpha and IL-6 mRNA and protein levels were observed in microglia, but not astrocytes, from SIGIRR-/- mice.
- SIGIRR deficiency resulted in more profound microglial activation, cytokine production, and accentuated behavioral effects in response to LPS.
- Increased hippocampal expression of CD14 and TLR4, and enhanced NF-kappaB activation were observed in SIGIRR-/- mice.
Conclusions:
- SIGIRR deficiency exacerbates LPS-induced neuroinflammation, particularly affecting microglia.
- SIGIRR plays a critical role in suppressing inflammatory responses within the brain.
- Increased CD14, TLR4, and NF-kappaB activation likely contribute to heightened neuroinflammation in SIGIRR-deficient mice.
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