ICAM-1

Yeah, a nice systematic review in the Journal of the Academy of Nutrition and Dietetics in 2012 looked at 15 randomized trials, which randomized people to higher linoleic acid intake versus other fats, and not a single one showed an increased C-reactive protein in the high linoleic acid group.

There was also no effect on IL-6, TNF-alpha, ICAM-1, LNP-selectin, fibrinogen, platelet activity, or any of the measured prostaglandins or thromboxane.

So if you have a favorite inflammatory marker-

Thrumboxine did cause me concern.

Both the P38 alpha MAP kinase and the neutral sphingomyelinase 2 are linked in the literature with TNF-alpha stimulated upregulation of adhesion molecules, proteins in particular.

That would include the vascular cell adhesion molecule 1, BCAM1, and the intracellular adhesion molecule that's called ICAM1.

And that's actually totally independent of the transcription factor N of kappa B, which normally controls the regulation of the expression of those adhesion proteins.

So what does that demonstrate? That the P38-MAF kinase functioning upstream of the neutral sphingomyelinase 2 is telling you that the neutral sphingomyelinase 2 is indeed a response to pro-inflammation initially induced by TNF-alpha.

So you probably want to reduce inflammation, get those tears filled with inflammatory mediators and toxic cytokines out of the eye.

either short-term steroids, transition to T-cell mediated or ICAM1 inhibitors, things that interfere with T-cells, then you can focus on getting the tears supplement in there that's going to give you a little bit more retention time.

But yes, I think from a very practical standpoint, anything that retains water is going to help Whether it's coming from the form of lack of tear production or from a lack of lipid in the tears, it's still going to give some help.

But again, as we already hinted, there is a generation of eye drops now that's adding in second, third, fourth types of elements that are trying to truly mimic the tri-layered tear film.

Now, lipoprotein lipase hydrolysis products generated from the VLDL fraction seem to be the ones that are associated to increase TNF-alpha secretion from the endothelial cells, and then increase intercellular adhesion molecule one.

That's the ICAM-1.

Remember this? ICAM-1 expressed at the transcriptional level, and then obviously the protein synthesized after translation.

Now, that occurs on the endothelial cells.

Now, in breast cancers, ICAM-1 is upregulated by TNF-alpha, and ICAM therefore seems to be involved, ICAM-1, in tumor cell invasion and metastasis.

It does so by promoting intravasation through the vasculature.

However, the role of lipoprotein utilization products generated by the LPL on cytokine secretion in breast cancer, that's a different process entirely.

So if you haven't figured out already, we're in the synthesis phase of these lectures.

I guess I got carried away with my prolegomena, right? [chuckles] Uh, what else we observed were surface ICAM.

So ICAM protein, ICAM-1 expression is, uh, is again on the surface of these cells, and that's following PCSK9 treatment.

You see a reduction in the ICAM on the surface.

And what is ICAM doing? Of course, yeah, next question is the function.

Well, it's required for cholesterol-rich lipid microdomains to stabilize in the membrane.

So that's a cholesterol protein interaction.

So you see reduced ICAM after treating with that convertase, and what, because the convertase obviously is also involved with altering many proteins on the surface of the plasma membrane of the cytotoxic T lymphocyte, like ICAM.

No primary A-landogen.

And without B7.2 and ICAM-1, the structural antenna is required to physically dock with the T-cell to deliver the secondary activation signal.

They're just missing.

They just don't have the hardware.

No primary A-landogen.

And without B7.2 and ICAM-1, the structural antenna is required to physically dock with the T-cell to deliver the secondary activation signal.

They're just missing.

They just don't have the hardware.