Leishmania donovani secretory serine protease alters macrophage inflammatory response via COX-2 mediated PGE-2 production.

Leishmania parasites determine the outcome of the infection by inducing inflammatory response that suppresses macrophage’s activation. Defense against Leishmania is dependent on Th1 inflammatory response by turning off macrophages’ microbicidal property by upregulation of COX-2, as well as immunosuppressive PGE-2 production. To understand the role of L. donovani secretory serine protease (pSP) in these phenomena, pSP was inhibited by its antibody and serine protease inhibitor, aprotinin. Western blot and TAME assay demonstrated that pSP antibody and aprotinin significantly inhibited protease activity in the live Leishmania cells and reduced infection index of L. donovani-infected macrophages. Additionally, ELISA and RT-PCR analysis showed that treatment with pSP antibody or aprotinin hold back COX-2-mediated immunosuppressive PGE-2 secretion with enhancement of Th1 cytokine like IL-12 expression. This was also supported in Griess test and NBT assay, where inhibition of pSP with its inhibitors elevated ROS and NO production. Overall, our study implies the pSP is involved in down-regulation of macrophage microbicidal activity by inducing host inflammatory responses in terms of COX-2-mediated PGE-2 release with diminished reactive oxygen species generation and thus suggests its importance as a novel drug target of visceral leishmaniasis.

A possible defective estimation of antineutrophil cytoplasmic antibodies in systemic lupus erythematosus due ot the coexistence of periodontitis: preliminary observations

The objectives of this study is to determine if periodontitis-related ANCA hinder the accurate estimation of this kind of autoantibodies in systemic lupus erythematosus (SLE), due to the frequent coexistence of SLE and periodontitis, and the high incidence of antineutrophil cytoplasmic antibodies (ANCA) in this periodontal condition. Thirty SLE, thirty periodontitis lacking systemic involvement patients, and twenty healthy controls were utilized in this study. The periodontal condition and the presence of ANCA in sera of all individuals was carefully evaluated. For ANCA determination an EIA essay was utilized, directed to a neutrophil granular extract and six neutrophil granule proteins. Sixty percent of SLE patients had periodontitis, and sixty-five percent were ANCA positive. Eighty three percent of all ANCA cases were coexisting with periodontitis. A significant association (p > 0.005) between periodontitis and ANCA was found (Chi Square Test). Fifty percent of the patients with periodontitis lacking systemic involvement were ANCA positive. The results obtained in this study suggest that the figures of ANCA previously reported for SLE, might be overestimated due to the inadvertent presence of periodontitis