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Lipopolysaccharide tolerance attenuates inflammatory responses by increasing heme oxygenase 1 and tristetraprolin expression in Raw264.7 macrophages

Akhi Moni.

Inflammation is associated with the progression of a variety of diseases. Lipopolysaccharides (LPS) tolerance is recognized to reduce proinflammatory responses. Heme oxygenase1 (HO1) and tristetraprolin (TTP) are induced by LPS tolerance and mediate the anti-inflammatory effects. However, it was not clear whether two molecules are linked in LPS tolerance. In this study, we sought to determine whether HO1 associates with TTP to mediate the anti-inflammatory effects of LPS tolerance. LPS treatment significantly increased mRNA and protein level of HO1 and TTP in a time dependant fashion while LPS significantly decreased mRNA and protein level of TNFα in Raw264.7 macrophages. LPS tolerance inhibited TNFα mRNA and protein while HO1 and TTP level was still increased. In HO1 deficient macrophages, LPS tolerance failed to attenuate TNFα mRNA expression but TTP level was still decreased. Our results suggest that HO1 and TTP are functionally linked in mediating anti-inflammatory effects of LPS tolerance. This novel LPS tolerance-HO1-TTP signaling pathway provides new possibilities for the treatment of inflammatory diseases.

Key words: LPS tolerance, anti-inflammatory effects, HO1, TTP

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The articles in Bibliomed are open access articles licensed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (https://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.