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Enhanced inflammatory responses in alpha-tocopherol transfer protein null mice
Bettina C Schock1, Albert Van der Vliet, Ana M Corbacho
1Division of Pulmonary and Critical Care Medicine and Center for Comparative Respiratory Biology and Medicine, University of California School of Medicine, Davis, CA 95616, USA.
Archives of Biochemistry and Biophysics
|February 12, 2004
Summary
Vitamin E (alpha-tocopherol) is crucial for regulating inflammatory responses. Vitamin E deficiency in mice altered immune cell function and inflammatory marker expression during inflammation.
Area of Science:
- Biochemistry
- Immunology
- Nutrition Science
Background:
- The liver regulates plasma alpha-tocopherol (Vitamin E) via alpha-tocopherol transfer protein (alpha-TTP).
- alpha-TTP-null mice (Ttpa(-/-)) exhibit vitamin E deficiency, providing a model for studying sub-normal vitamin E levels.
- Increased oxidative stress is a hallmark of vitamin E deficiency.
Purpose of the Study:
- To investigate the in vivo inflammatory and immune responses in vitamin E-deficient mice.
- To determine the role of alpha-tocopherol in modulating oxidative stress and inflammatory markers during inflammation.
Main Methods:
- Utilized alpha-TTP-null (Ttpa(-/-)) and wild-type (Ttpa(+/+)) mice.
- Assessed basal oxidative stress via plasma lipid peroxidation and neutrophil superoxide production.
- Induced inflammation using intraperitoneal lipopolysaccharide (LPS) injection.
- Measured inflammatory markers including HO-1, iNOS, NO(x), IL-10, and TNF alpha in various tissues and plasma.
Main Results:
- Ttpa(-/-) mice showed increased basal oxidative stress compared to Ttpa(+/+) mice.
- LPS challenge induced distinct inflammatory profiles in Ttpa(-/-) versus Ttpa(+/+) mice.
- While Ttpa(-/-) mice had attenuated increases in some inflammatory markers (HO-1, iNOS, NO(x)), they exhibited elevated plasma IL-10 and lung TNF alpha.
Conclusions:
- Alpha-tocopherol plays a significant role in the appropriate modulation of inflammatory and immune responses.
- Sub-optimal vitamin E concentrations can lead to dysregulated inflammatory-immune reactions.
- These findings highlight the importance of adequate vitamin E status for maintaining immune homeostasis during inflammatory conditions.