Ahn YH, Jeon SB, Chang CY, Goh EA, Kim SS, Kim HJ, Song J, Park EJ.Glatiramer acetate attenuates the activation of CD4+ T cells by modulating STAT1 and -3 signaling in glia.
Sci Rep. 2017 Jan 17;7:40484
Interactions between immune effector cells of the central nervous system appear to directly or indirectly influence the progress/regression of multiple sclerosis (MS). Here, we report that glial STAT1 and -3 are distinctively phosphorylated following the interaction of activated lymphocytes and glia, and this effect is significantly inhibited by glatiramer acetate (GA), a disease-modifying drug for MS. GA also reduces the activations of STAT1 and -3 by MS-associated stimuli such as IFNγ or LPS in primary glia, but not neurons. Experiments in IFNγ- and IFNγ receptor-deficient mice revealed that GA-induced inhibitions of STAT signaling are independent of IFNγ and its receptor. Interestingly, GA induces the expression levels of suppressor of cytokine signaling-1 and -3, representative negative regulators of STAT signaling in glia. We further found that GA attenuates the LPS-triggered enhancement of IL-2, a highly produced cytokine in patients with active MS, in CD4+ T cells co-cultured with glia, but not in CD4+ T cells alone. Collectively, these results provide that activation of glial STATs is an essential event in the interaction between glia and T cells, which is a possible underlying mechanism of GA action in MS. These findings provide an insight for the development of targeted therapies against MS
Is it really a new mechanism?
Not really as GA has always been inhibiting T cells hasn't it?
STAT1 and STAT3 are transcription factor i.e. they affect the production levels of proteins from the DNA.
The study says that GA reduces the effect of the STATS in response to interferon gamma and LPS. LPS is lipopolysaccharide a sugar like molecule on bacteria...So this implies that MS is caused by bacteria!.
They examine the effect of glia....in this case it is usually a mix of microGLIA and astroGLIA but they do experiments in single cell types too.
It states "All animal procedures were performed according to the ARRIVE guidelines". However the ARRIVE guidelines are a reporting guideline, not a how to do experiments guideline.
So it shows how good the referees and editors are:-)
However, is this real? Why because the glatiramer acetate was from a chemical supply company and not the real McCoy. So is this generic any good.
COI : None
Labels: glatiramer acetate