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Phlebotomine salivas inhibit immune inflammation‐induced neutrophil migration via an autocrine DC‐derived PGE 2 /IL‐10 sequential pathway
Author(s) -
Carregaro Vanessa,
Valenzuela Jesus G.,
Cunha Thiago M.,
Verri Waldiceu A.,
Grespan Renata,
Matsumura Graziela,
Ribeiro José M. C.,
Elnaiem DiaEldin,
Silva João S.,
Cunha Fernando Q.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1107797
Subject(s) - biology , immune system , immunology , inflammation , autocrine signalling , leukotriene b4 , receptor , biochemistry
In the present study, we investigated whether saliva from Phlebotomus papatasi and Phlebotomus duboscqi inhibited antigen‐induced neutrophil migration and the mechanisms involved in these effects. The pretreatment of immunized mice with salivary gland extracts (SGE) of both phlebotomines inhibited OVA challenge‐induced neutrophil migration and release of the neutrophil chemotactic mediators, MIP‐1α, TNF‐α, and leukotriene B 4 (LTB 4 ). Furthermore, SGE treatment enhanced the production of anti‐inflammatory mediators, IL‐10 and PGE 2 . SGE treatments failed to inhibit neutrophil migration and MIP‐1α and LTB 4 production in IL‐10 −/− mice, also failing in mice treated with nonselective (indomethacin) or selective (rofecoxibe) cyclooxygenase (COX) inhibitors. COX inhibition resulted in diminished SGE‐induced IL‐10 production, and PGE 2 release triggered by SGE remained increased in IL‐10 −/− mice, suggesting that prostanoids are acting through an IL‐10‐dependent mechanism. SGE treatments in vivo reduced the OVA‐induced lymphoproliferation of spleen‐derived cells. Further, the in vitro incubation of bone marrow‐derived dendritic cells (DC) with SGE inhibited the proliferation of CD4 + T cells from OVA‐immunized mice, which was reversed by indomethacin and anti‐IL‐10 antibody treatments. Supporting these results, SGE induced the production of PGE 2 and IL‐10 by DC, which were blocked by COX inhibition. These effects were associated with the reduction of DC‐membrane expression of MHC‐II and CD86 by SGE treatment. Altogether, the results showed that Phlebotomine saliva inhibits immune inflammation‐induced neutrophil migration by an autocrine DC sequential production of PGE 2 /IL‐10, suggesting that the saliva constituents might be promising therapeutic molecules to target immune inflammatory diseases.