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Resolvins activate inflammation-resolution programs: a systems approach to resolution
A selection of talks on Biochemistry
The ERK1/2 MAPK cascade
- Prof. Melanie H. Cobb
- University of Texas Southwestern Medical Center at Dallas, USA
Amino acid conjugation: mechanism and enzymology
- Dr. Kathleen Knights
- Flinders University, Australia
My name is Charles Serhan, and this is the second part of our Henry Stewart talk series under the innate immunity series. And this is part two. Part one was novel lipid mediators and resolution of inflammation. And since this is a very rapidly moving area with a lot of excitement presently. We thought it would be apropos to update this with a second lecture, which is entitled Resolvins Activate Inflammation-Resolution Programs, A Systems Approach to Resolution. And I will review the main points from the first lecture in case you don't have an opportunity to listen to it.
My institution requires that I show this disclosure slide from our NIH supported research grants. Intellectual property has evolved. That has led to licensing of patents to both Bayer Healthcare and to Resolvyx Pharmaceuticals. And from this identification of novel mediators that are involved in resolution, I was a founder and co founder of Resolvyx Pharmaceutical. And the mission of this company is to take this information in modules from bench to clinic.
So, we now know that there are many different lipid mediators that play a role in resolution. And this slide depicts the main sites of action of this new genus of pro-resolvin lipid mediators and their unique mechanism of action. These, as you know from the first lecture, are biosynthesized from essential fatty acids. And this genus constitutes several families of structurally distinct molecules that we'll go over in this presentation. The lipoxins, the resolvins, and the protectins. They act on both leukocytes, neutrophils, depicted here in their diapedesis, one of the first committed steps to acute inflammatory response. As well as stimulating pro-resolvin responses on macrophages, for example, and their ability to enhance the uptake of apoptotic neutrophils by macrophages. Clear them so that they can eflux and clear debris as well to lymphatics. So, these families of lipid mediators have as their unique function the ability to carry anti-inflammatory as well as pro-resolvin actions. Now, we've introduced resolution indices to precisely pinpoint the site of action and to quantitate this pro-resolvin action which had not been subject to interrogation earlier. And in the course of this, we've learned that there are pro-resolvin mediators, which we call the maresins, that also act like resolvins that are brought in late in the resolution response.