| First Author | Riquelme SA | Year | 2015 |
| Journal | Immunology | Volume | 144 |
| Issue | 2 | Pages | 321-32 |
| PubMed ID | 25179131 | Mgi Jnum | J:220097 |
| Mgi Id | MGI:5632234 | Doi | 10.1111/imm.12375 |
| Citation | Riquelme SA, et al. (2015) Carbon monoxide down-modulates Toll-like receptor 4/MD2 expression on innate immune cells and reduces endotoxic shock susceptibility. Immunology 144(2):321-32 |
| abstractText | Carbon monoxide (CO) has been recently reported as the main anti-inflammatory mediator of the haem-degrading enzyme haem-oxygenase 1 (HO-1). It has been shown that either HO-1 induction or CO treatment reduces the ability of monocytes to respond to inflammatory stimuli, such as lipopolysaccharide (LPS), due to an inhibition of the signalling pathways leading to nuclear factor-kappaB, mitogen-activated protein kinases and interferon regulatory factor 3 activation. Hence, it has been suggested that CO impairs the stimulation of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD2) complex located on the surface of immune cells. However, whether CO can negatively modulate the surface expression of the TLR4/MD2 complex in immune cells remains unknown. Here we report that either HO-1 induction or treatment with CO decreases the surface expression of TLR4/MD2 in dendritic cells (DC) and neutrophils. In addition, in a septic shock model of mice intraperitoneally injected with lipopolysaccharide (LPS), prophylactic treatment with CO protected animals from hypothermia, weight loss, mobility loss and death. Further, mice pre-treated with CO and challenged with LPS showed reduced recruitment of DC and neutrophils to peripheral blood, suggesting that this gas causes a systemic tolerance to endotoxin challenge. No differences in the amount of innate cells in lymphoid tissues were observed in CO-treated mice. Our results suggest that CO treatment reduces the expression of the TLR4/MD2 complex on the surface of myeloid cells, which renders them resistant to LPS priming in vitro, as well as in vivo in a model of endotoxic shock. |
