Open AccessMacrophage release of transforming growth factor β1 during resolution of monosodium urate monohydrate crystal–induced inflammation
Author(s) -
Yagnik Darshna R.,
Evans Betsy J.,
Florey Oliver,
Mason Justin C.,
Landis R. Clive,
Haskard Dorian O.
Publication year - 2004
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.20317
Subject(s) - proinflammatory cytokine , tumor necrosis factor alpha , monocyte , macrophage , inflammation , cd14 , microbiology and biotechnology , chemistry , immunology , in vitro , immune system , biology , biochemistry
Objective It has previously been shown that as monocytes differentiate into macrophages, they lose the ability to secrete proinflammatory cytokines in response to monosodium urate monohydrate (MSU) crystals. The purpose of this study was to investigate whether MSU crystals induce macrophages to secrete antiinflammatory factor instead. Methods Human monocyte or macrophage isolates were prepared from samples obtained from healthy volunteer donors either by differentiation of blood monocytes in vitro or by collecting cells from skin blisters during the early or late phase of the dermal inflammatory response to cantharidin. Monocyte or macrophage isolates were then incubated with MSU crystals for 24 hours, and culture supernatants were assayed for candidate antiinflammatory mediators (by enzyme‐linked immunosorbent assay) and for the capacity to activate or suppress endothelial cell E‐selectin expression and secondary neutrophil recruitment under shear flow. Results Analysis of supernatants from in vitro–differentiated macrophages revealed that transforming growth factor β1 (TGFβ1) was induced following MSU crystal stimulation (mean ± SEM 1.50 ± 0.24 ng/ml/10 6 cells), but there was no evidence of interleukin‐10 (IL‐10), IL‐1 receptor antagonist, or tumor necrosis factor (TNF) receptor p55 release. Macrophage TGFβ1 significantly suppressed endothelial cell E‐selectin expression and secondary neutrophil capture on endothelial monolayers stimulated with supernatants from MSU‐treated monocytes. Leukocytes isolated from resolving (40‐hour) skin blisters similarly elaborated TGFβ1 when challenged with MSU crystals (0.66 ± 1.3 ng/ml/10 5 CD14+ cells). In contrast, cells isolated from acute (16‐hour) skin blisters secreted TNFα (0.49 ± 0.08 ng/ml/10 5 CD14+ cells) but no detectable TGFβ1. Conclusion These data provide further support for the concept that differentiated macrophages play a protective role in the pathophysiology of gout, and they identify macrophage TGFβ1 as a mediator of paracrine suppression during the resolution phase of inflammation.