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Printable Handouts
Navigable Slide Index
- Introduction
- Disclosures for Charles N. Serhan
- New genus for pro-resolving lipid mediators
- Resolvins & protectins
- Metabolomics towards human treatment
- Talk outline - focus on human translation
- Decision paths in acute Inflammation
- Human neutrophils - 1st line host defense
- Murine air pouch model
- Systems approach mapping resolution
- Lipid mediator - lipidomics informatics
- Lipid mediator profiling, matching and validation
- Ideal inflammation outcome - complete resolution
- Acute phase to resolution phase
- Effects of Aspirin
- Resolvin E1 - biosynthesis, stereochemistry, MOI
- Resolvins and Protectins - new mediator families
- DHA metabolome
- Biosynthesis of E series resolvins in humans
- Pro-resolving - a new bioaction of SPM
- Pro-resolving lipid mediators
- What impacts the resolution interval in vivo
- Potent protection in animal diseases
- Failure of resolution in inflammatory diseases
- RvE1 and RvD1 attenuate inflammatory pain
- Resolvin E1 (RvE1) pathway
- RvE1 receptor ChemR23 neuronal expression
- RvE metabolome
- 19-para-fluoro-phenoxyl RvE1
- CFA-induced heat hyperalgesia
- Biosynthesis of RvD2
- RvD2 - stereochemistry and double bond geometry
- RvD2 potently reduces microbial peritonitis
- Pathogenesis of sepsis
- Caecal ligation and puncture
- RvD2 decreases Pro-inflammatory mediators
- RvD2 modulates cytokines, chemokines in sepsis
- RvD2 protects from CLP-induced sepsis
- RvD2 reduces local and systemic bacterial burden
- RvD2 - bacteria containment in lymph node
- RvD2 - enhanced phagocytosis, ROS generation
- Key concepts & points
- Novel microfluidics chamber
- RvD1 stops PMN chemotaxis
- RvE1, RvD1 do not activate nuclear receptors
- RvD1 - specific binding to human PMN
- RvD1 effects exerted via GPR32, ALF/FPR2
- RvD1 and LXA4 activate human GPR32 receptor
- Temporal regulation of miRNAs in resolution
- Effects of RvD1 in resolving exudate
- RvD1 regulates expression of specific miRNAs
- RvD1 controls miRNAs via human GPCRs
- Resolution circuits - resolvins and miRNAs
- RvD1-GPCR-dependent miRNAs
- Effects of miR-219 overexpression in macrophages
- RvD1 - schematic signaling pathway
- Self-limited evolving exudate
- Resolvins - agonists that stimulate resolution
- RvD1-GPCR miRNAs resolution
- Conclusions
- Acknowledgments (1)
- Acknowledgments (2)
Topics Covered
- New genus for pro-resolving lipid mediators
- Resolvins & protectins
- Metabolomics towards human treatment
- Decision paths in acute Inflammation
- Systems approach mapping resolution
- Ideal inflammation outcome- complete resolution
- Acute phase to resolution phase
- Effects of Aspirin
- Resolvins and Protectins- new mediator families
- DHA metabolome
- Pro-resolving lipid mediators
- Resolution interval and failure of resolution in inflammatory diseases
- RvE1 and RvD1- biosynthesis, structure and action
- Pathogenesis of sepsis
- RvD2, RvE1, RvD1 effects in inflammation
- Self-limited evolving exudate
- Resolvins are agonists that stimulate resolution
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Talk Citation
Serhan, C. (2020, May 1). Resolvins activate inflammation-resolution programs: a systems approach to resolution [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/VURW2652.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Charles Serhan has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Resolvins activate inflammation-resolution programs: a systems approach to resolution
A selection of talks on Biochemistry
Transcript
Please wait while the transcript is being prepared...
0:00
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.
0:49
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.
1:34
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.
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