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Therapeutic intervention of monocytes to LPS challenge

ABSTRACT: To investigate the possible therapeutic effects of ibuprofen and Pep19-2.5 alone or in combination on the LPS-response of human monocytes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE65855 | GEO | 2015/07/02

SECONDARY ACCESSION(S): PRJNA275231

REPOSITORIES: GEO

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Therapeutic intervention of monocytes to LPS challenge

Project description:To investigate the possible therapeutic effects of ibuprofen and Pep19-2.5 alone or in combination on the LPS-response of human monocytes. Human monocytes were challenged with 0.1ng/ml LPS and/or 10ng/ml Pep19-2.5 LPS. Medium controls served as unstimulated samples. LPS and Pep19-2.5 was used either alone or together to LPS-challenged samples. RNA was extracted after 4 hrs of stimulation. Three biological replicates were conducted

2015-07-02 | E-GEOD-65855 | biostudies-arrayexpress

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Project description:Lipopolysaccharide (LPS) can either promote or prevent T helper-2 (Th2) cell-allergic responses. However, the underlying mechanism remains unknown. We show here that LPS activity switches from pro-pathogenic to protective depending on the production of GM-CSF by non-classical monocytes. In the absence of GM-CSF, LPS can favor pathogenic Th2 cell responses by supporting the trafficking of lung migratory dendritic cells (mDC2s) into the lung-draining lymph node. However, when non-classical monocytes produce GM-CSF, LPS and GM-CSF synergize to differentiate monocyte-derived DCs (moDCs) that instruct mDC2s for Th2 cell suppression. Importantly, only allergens with cysteine protease activity trigger GM-CSF production by non-classical monocytes. Hence, the therapeutic effect of LPS is restricted to allergens with this enzymatic activity. Treatment with GM-CSF, however, restores the protective effects of LPS. Thus, GM-CSF produced by non-classical monocytes acts as a rheostat that fine-tunes the pathogenic and therapeutic functions of LPS.

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