Urate crystals induce macrophage PAF ‑AH secretion which is differentially regulated by TGFβ1 and hydrocortisone.

Urate crystals induce macrophage PAF‑AH secretion which is differentially regulated by TGFβ1 and hydrocortisone. Mol Med Rep. 2018 Jul 26;: Authors: Yagnik D, Hills F Abstract The aim of the present study was to establish the role of platelet‑activating factor acetyl hydrolase (PAF‑AH) in the resolution phase of gout using an established in vitro mononuclear cell model. The effects of signalling pathway inhibitors on PAF‑AH secretion, as well as the effects of the common treatments hydrocortisone and colchicine, an antibody against the anti‑inflammatory cytokine transforming growth factor β1 (TGFβ1), and the transcriptional inhibitor actinomycin D, were also investigated. The effect of recombinant PAF‑AH on cytokine secretion by these cells was also determined. Human peripheral blood‑derived monocytes were isolated and differentiated into macrophages. Monocytes and macrophages were stimulated with monosodium monohydrate urate (MSU) crystals or lipopolysaccharide in the presence or absence of AEG3482 [a c‑Jun N‑terminal kinase (JNK) inhibitor], MG132 (a proteasome inhibitor), hydrocortisone or colchicine. Cultures were then analysed for PAF‑AH secretion using ELISA. A 6‑fold upregulation of PAF‑AH secretion was observed following macrophage exposure to MSU crystals for 24 h (29.3±6 vs. 5.4±0.3 ng/ml unstimulated; P<0.05). Following 72 h, PAF‑AH levels decreased significantly (11.1±1.8; P<0.0...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research