Abstract

BackgroundActivity of secreted phospholipase A (sPLA2) has been implicated in a wide range of cellular responses. However, little is known about the function of human parvovirus B19-VP1 unique region (VP1u) with sPLA2 activity on macrophage.MethodsTo investigate the roles of B19-VP1u in response to macrophage, phospholipase A2 activity, cell migration assay, phagocytosis activity, metalloproteinase assay, RT-PCR and immunoblotting were performed.ResultsIn the present study, we report that migration, phagocytosis, IL-6, IL-1β mRNA, and MMP9 activity are significantly increased in RAW264.7 cells by B19-VP1u protein with sPLA2 activity, but not by B19-VP1uD175A protein that is mutated and lacks sPLA2 activity. Additionally, significant increases of phosphorylated ERK1/2 and JNK proteins were detected in macrophages that were treated with B19-VP1u protein, but not when they were treated with B19-VP1uD175A protein.ConclusionTaken together, our experimental results suggest that B19-VP1u with sPLA2 activity affects production of IL-6, IL-1β mRNA, and MMP9 activity, possibly through the involvement of ERK1/2 and JNK signaling pathways. These findings could provide clues in understanding the role of B19-VP1u and its sPLA2 enzymatic activity in B19 infection and B19-related diseases.

Highlights

  • Activity of secreted phospholipase A has been implicated in a wide range of cellular responses

  • Recombinant B19-VP1 unique region (VP1u) proteins reveal sPLA2 activity Recent studies have demonstrated that B19-VP1u possesses phospholipase A2 (PLA2) activity that is postulated to be involved in a variety of inflammatory reactions [811]

  • Apparent sPLA2 activity was detected in the recombinant B19-VP1u protein with an activity of 0.19 ± 0.03 μmol/min/mL, as well as bvPLA2 which is considered as a positive control with an activity of 0.56 ± 0.12 μmol/min/mL

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Summary

Introduction

Activity of secreted phospholipase A (sPLA2) has been implicated in a wide range of cellular responses. Little is known about the function of human parvovirus B19-VP1 unique region (VP1u) with sPLA2 activity on macrophage. The icosahedral capsid consists of two structural proteins, VP1 (83 kDa) and VP2 (58 kDa), which are identical with the exception of 227 amino acids at the amino-terminal end of the VP1-protein, the so-called VP1-unique region (VP1u) [3]. Journal of Biomedical Science 2009, 16:13 http://www.jbiomedsci.com/content/16/1/13 immunizing rabbits with a fusion protein containing the entire unique region sequence of VP1 neutralized the binding activity of B19 [7]. Parvovirus PLA2 has been classified as a group XIII PLA2 [10,13], the precise function of secreted phospholipases A (sPLA2) from B19-VP1u is still obscure

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