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Regulation of type V phospholipase A2 expression and function by proinflammatory stimuli
H Sawada1, M Murakami, A Enomoto
1Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
European Journal of Biochemistry
|September 1, 1999
Summary
Secretory phospholipase A2-V (sPLA2-V) regulates inflammation by increasing prostaglandin generation and cellular responses. This may compensate for sPLA2-IIA, explaining minimal impact in gene-disrupted mice.
Area of Science:
- Biochemistry
- Immunology
- Molecular Biology
Background:
- Secretory phospholipase A2-IIA (sPLA2-IIA) is known to augment prostaglandin generation during inflammation.
- The functional regulation and role of the related secretory phospholipase A2-V (sPLA2-V) in inflammatory processes remain largely uncharacterized.
Purpose of the Study:
- To investigate the role and mechanism of sPLA2-V in inflammation-associated cellular responses.
- To compare the expression patterns and functional significance of sPLA2-V and sPLA2-IIA.
Main Methods:
- Comparative analysis of sPLA2-V and sPLA2-IIA gene expression in mouse and rat models.
- Cotransfection studies in human embryonic kidney 293 cells to assess the interaction of sPLA2-V with cyclooxygenase enzymes (COX-1 and COX-2).
- Overexpression studies in rat mastocytoma RBL-2H3 cells to evaluate sPLA2-V's effect on IgE-dependent responses.
Main Results:
- sPLA2-V exhibits broader expression than sPLA2-IIA in mice and is upregulated by lipopolysaccharide (LPS).
- Proinflammatory stimuli preferentially induce sPLA2-IIA over sPLA2-V in rats.
- Cotransfection of sPLA2-V with COX-2, but not COX-1, significantly enhanced interleukin-1-dependent PGE2 generation.
- Overexpression of sPLA2-V in RBL-2H3 cells increased PGD2 generation and accelerated beta-hexosaminidase release.
Conclusions:
- sPLA2-V plays a significant role in regulating inflammation-associated cellular responses, including prostaglandin synthesis and mediator release.
- sPLA2-V may functionally compensate for sPLA2-IIA in various tissues, potentially explaining the lack of severe phenotypes in sPLA2-IIA gene-disrupted mice.