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Angiopoietin‐1 but not angiopoietin‐2 induces IL‐8 synthesis and release from human neutrophils
Author(s) -
Neagoe PaulEduard,
Dumas Elizabeth,
Hajjar Fadi,
Sirois Martin G
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb61
Subject(s) - cycloheximide , messenger rna , chemistry , p38 mitogen activated protein kinases , angiopoietin , mapk/erk pathway , chemotaxis , protein synthesis inhibitor , protein biosynthesis , protein kinase c , receptor , interleukin 8 , protein kinase a , kinase , microbiology and biotechnology , cytokine , medicine , biochemistry , biology , immunology , gene , vascular endothelial growth factor , vegf receptors
Angiopoietins (Ang1 and Ang2) can promote neutrophil chemotactic activities by activating Tie2 receptor. Moreover, pretreatment with Ang1 or Ang2 enhances the chemotactic effect of interleukin‐8 (IL‐8). We wanted to assess if angiopoietins can promote IL‐8 protein synthesis and release from human neutrophils. Only a treatment with Ang1 at 10 −8 M induced a significant increase of IL‐8 protein synthesis (3.6‐fold) and release (5.5‐fold), whereas the combination of Ang1 and Ang2 induced the same effect as Ang1 alone. Moreover, IL‐8 mRNA production was also increased (4.7‐fold) as compared to PBS. Cycloheximide, a protein synthesis inhibitor, reduced Ang1‐mediated IL‐8 protein synthesis and release by up to 96 and 92% respectively, whereas IL‐8 mRNA was increased by up to 18‐fold compared to PBS‐treated neutrophils. Actinomycin D, an mRNA synthesis inhibitor, reduced Ang1‐mediated IL‐8 mRNA and protein synthesis only within the first hour of treatment by 54 and 52% respectively. Using specific kinase inhibitors, we observed that Ang1‐driven IL‐8 mRNA and protein increase is p42/44 MAPK dependent and independent from p38 MAPK and PI3K activity. In summary, Ang1 (10 −8 M) induces IL‐8 mRNA synthesis, as well as IL‐8 protein synthesis and release, through the activation of p42/44 MAPK. This work was supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Quebec.