Zusammenfassung
Our earlier studies indicated that activation of the lymphotoxin beta receptor (LT beta R) by T cell derived LT alpha(1)beta(2) regulates inflammatory cytokine expression. While characterizing the cellular and molecular mechanisms responsible for the down regulation of the inflammatory reaction after LT beta R stimulation we were able to identify the specific induction of TRIM30 alpha expression ...
Zusammenfassung
Our earlier studies indicated that activation of the lymphotoxin beta receptor (LT beta R) by T cell derived LT alpha(1)beta(2) regulates inflammatory cytokine expression. While characterizing the cellular and molecular mechanisms responsible for the down regulation of the inflammatory reaction after LT beta R stimulation we were able to identify the specific induction of TRIM30 alpha expression as a result of LT beta R signalling in mouse macrophages. Furthermore, we could demonstrate that LT beta R activation in these cells results in the down regulation of pro-inflammatory cytokine (e.g. TNF and IL-6) and mediator expression upon TLR4 and TLR9 re-stimulation, demonstrating that LT beta R activation on mouse macrophages dampens pro-inflammatory cytokine and mediator expression. Thus, LT beta R signalling renders macrophages hypo-responsive to subsequent stimulation with TLR ligands. The observation of an LT beta R-mediated TLR-tolerance in the human monocyte cell line THP-1 suggests that similar signalling mechanisms seem to exist in human cells. Signalling pathway analysis clearly demonstrated that LT beta R-induced TRIM30 alpha expression is mediated by an I kappa B alpha-dependent signalling pathway. Furthermore, the LT beta R-induced TRIM30 alpha expression seems to be TRAF3 dependent. Our data suggest that LT beta R activation on mouse macrophages is involved in the control of pro-inflammatory cytokine and mediator expression by activation of a signalling pathway that controls exacerbating inflammatory cytokine production. (C) 2012 Elsevier Ltd. All rights reserved.
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