Oncolix Inc. (fka ONCX)

[WeeZuhl]

New Lupus research using Prolanta



https://www.mdpi.com/2073-4409/10/2/316/pdf

Cells 2021, 10, 316.
Article
Prolactin Rescues Immature B Cells from Apoptosis-Induced
BCR-Aggregation through STAT3, Bcl2a1a, Bcl2l2, and Birc5
in Lupus-Prone MRL/lpr Mice

Received: 28 November 2020
Accepted: 24 January 2021
Published: 4 February 2021

2. Materials and Methods

2.3. Prolactin Hormone and Inhibitors
We used murine recombinant PRL (National Hormone and Peptide Program, NIH).
PRL receptor activation was ablated with an inhibitor (PRL-inh, G129R), a recombinant
analog of the PRL with a single amino acid substitution to create an antagonist of the
PRL receptor, which was donated by the manufacturer (Oncolix, Houston, Tex, USA) [22].
Stattic (Cell Signaling Technology, Danvers, MA, USA) is a nonpeptidic selective STAT3
inhibitor. This small molecule prevents the binding of tyrosine-phosphorylated peptide
motifs to the STAT3 SH2 domain [23].

Long story short, prolactin receptor is expressed in all B cells, but its expression is increased in the type of B cells that are implicated in the development of lupus. Prolactin binding to these receptors seems to rescue those cells from the suicide pathway, thus increasing lupus-type reactions. If "Prolanta" is used to inhibit binding of prolactin with its receptor, then potential lupus cells proceed through the cell suicide cycle.

These are just mouse cell studies, but the suggestion is that prolactin inhibitors like Prolanta could slow or prevent progression of lupus. Lupus is an auto-immune condition that affects millions of people world-wide, mostly women. It can be highly debilitating and is a frequent cause of kidney failure. There are currently no cures or effective treatments for lupus, except for long-term steroids, which then results in a whole slew of steroid-induced complications.

We found that all B cell maturation stages
in bone marrow express the prolactin receptor long isoform, in both wild-type and MRL/lpr mice,
but its expression increased only in the immature B cells of the latter, particularly at the onset of lupus.
In these cells, activation of the prolactin receptor promoted STAT3 phosphorylation and upregulation
of the antiapoptotic Bcl2a1a, Bcl2l2, and Birc5 genes. STAT3 binding to the promoter region of these
genes was confirmed through chromatin immunoprecipitation. Furthermore, inhibitors of prolactin
signaling and STAT3 activation abolished the prolactin rescue of self-engaged MRL/lpr immature B
cells. These results support a mechanism in which prolactin participates in the emergence of lupus
through the rescue of self-reactive immature B cell clones from central tolerance clonal deletion
through the activation of STAT3 and transcriptional regulation of a complex network of genes related
to apoptosis resistance.