vitamin D, antimicrobial peptides, CWD, and psuedomonas

[Guest guest]

Pippit recently posted an article, which I will include at the end

of this post, citing 1,25-D's role in upregulating something

called " cationic antimicrobrial peptides. "

These have been discussed on this list previously, because of their

ability to weaken the outer membranes of antibiotic-resistant CWD

bacteria. H. and I both found researchers talking about the use

of such peptides, adminstered together with antibiotics, to create a

kind of one-two punch: the peptides weaken the membrane, the abx get

in to finish the job.

[That I can remember this amazes me, and makes me think my current

treatment course is showing some real benefit].

So I decided to take a look at the related articles on Pub Med, and

found one suggesting that these peptides also have a particular

effectiveness against one of the pathogens Tony's taught us about,

pseudomonas - which makes me think perhaps vitamin D would be

helpful for patients fighting that bug, as well (it's the end of the

abstract).

***************************************************************

J Immunol. 2004 Sep 1;173(5):2909-12.

Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of

antimicrobial peptide gene expression.

Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-

Mendoza L, Lin R, Hanrahan JW, Mader S, White JH.

Department of Physiology, McGill University, Montreal, Quebec,

Canada.

The hormonal form of vitamin D(3), 1,25-dihydroxyvitamin D(3) (1,25

(OH)(2)D(3)), is an immune system modulator and induces expression

of the TLR coreceptor CD14.

1,25(OH)(2)D(3) signals through the vitamin D receptor, a ligand-

stimulated transcription factor that recognizes specific DNA

sequences called vitamin D response elements.

In this study, we show that 1,25(OH)(2)D(3) is a direct regulator of

antimicrobial innate immune responses. The promoters of the human

cathelicidin antimicrobial peptide (camp) and defensin beta2 (defB2)

genes contain consensus vitamin D response elements that mediate 1,25

(OH)(2)D(3)-dependent gene expression.

1,25(OH)(2)D(3) induces antimicrobial peptide gene expression in

isolated human keratinocytes, monocytes and neutrophils, and human

cell lines, and 1,25(OH)(2)D(3) along with LPS synergistically

induce camp expression in neutrophils.

Moreover, 1,25(OH)(2)D(3) induces corresponding increases in

antimicrobial proteins and secretion of antimicrobial activity

against pathogens including Pseudomonas aeruginosa. 1,25(OH)(2)D(3)

thus directly regulates antimicrobial peptide gene expression,

revealing the potential of its analogues in treatment of

opportunistic infections.

PMID: 15322146 [PubMed - indexed for MEDLINE]

************************************************************

Now, here's the article Pippit posted. I'm reposting it because I

think it's actual content quickly got lost in debating the MP, and

deserve attention for it's own sake (again, paragraph breaks added):

*************************************************************

FASEB J. 2005 Jul;19(9):1067-77.

Human cathelicidin antimicrobial peptide (CAMP) gene is a direct

target of the vitamin D receptor and is strongly up-regulated in

myeloid cells by 1,25-dihydroxyvitamin D3.

Gombart AF, Borregaard N, Koeffler HP.

Department of Medicine, Division of Hematology/Oncology, Cedars-

Sinai Medical Center, Geffen School of Medicine at UCLA, Los

Angeles, California 90048, USA. gombarta@...

The innate immune system of mammals provides a rapid response to

repel assaults from numerous infectious agents including bacteria,

viruses, fungi, and parasites.

A major component of this system is a diverse combination of

cationic antimicrobial peptides that include the alpha- and beta-

defensins and cathelicidins.

In this study, we show that 1,25-dihydroxyvitamin D3 and three of

its analogs induced expression of the human cathelicidin

antimicrobial peptide (CAMP) gene.

This induction was observed in acute myeloid leukemia (AML),

immortalized keratinocyte, and colon cancer cell lines, as well as

normal human bone marrow (BM) -derived macrophages and fresh BM

cells from two normal individuals and one AML patient.

The induction occurred via a consensus vitamin D response element

(VDRE) in the CAMP promoter that was bound by the vitamin D receptor

(VDR). Induction of CAMP in murine cells was not observed and

expression of CAMP mRNA in murine VDR-deficient bone marrow was

similar to wild-type levels.

Comparison of mammalian genomes revealed evolutionary conservation

of the VDRE in a short interspersed nuclear element or SINE in the

CAMP promoter of primates that was absent in the mouse, rat, and

canine genomes. Our findings reveal a novel activity of 1,25-

dihydroxyvitamin D3 and the VDR in regulation of primate innate

immunity.

PMID: 15985530 [PubMed - in process]

***************************************************************

Pippit, I am very curious what you make of these findings, and

whether they don't give you pause about treating what the mp.com

site characterizes as CWD-linked illness with a regimen of D-

deprivation.

> For those interested in the Vitamin D receptor and its

relationship

> to 1,25-D, here is another article;

>

> FASEB J. 2005 Jul;19(9):1067-77.

>

> Human cathelicidin antimicrobial peptide (CAMP) gene is a direct

> target of the vitamin D receptor and is strongly up-regulated in

> myeloid cells by 1,25-dihydroxyvitamin D3.

>

> Gombart AF, Borregaard N, Koeffler HP.

>

> Department of Medicine, Division of Hematology/Oncology, Cedars-

Sinai

> Medical Center, Geffen School of Medicine at UCLA, Los

Angeles,

> California 90048, USA. gombarta@c...

>

> The innate immune system of mammals provides a rapid response to

> repel assaults from numerous infectious agents including bacteria,

> viruses, fungi, and parasites. A major component of this system is

a

> diverse combination of cationic antimicrobial peptides that

include

> the alpha- and beta-defensins and cathelicidins. In this study, we

> show that 1,25-dihydroxyvitamin D3 and three of its analogs

induced

> expression of the human cathelicidin antimicrobial peptide (CAMP)

> gene. This induction was observed in acute myeloid leukemia (AML),

> immortalized keratinocyte, and colon cancer cell lines, as well as

> normal human bone marrow (BM) -derived macrophages and fresh BM

cells

> from two normal individuals and one AML patient. The induction

> occurred via a consensus vitamin D response element (VDRE) in the

> CAMP promoter that was bound by the vitamin D receptor (VDR).

> Induction of CAMP in murine cells was not observed and expression

of

> CAMP mRNA in murine VDR-deficient bone marrow was similar to wild-

> type levels. Comparison of mammalian genomes revealed evolutionary

> conservation of the VDRE in a short interspersed nuclear element

or

> SINE in the CAMP promoter of primates that was absent in the

mouse,

> rat, and canine genomes. Our findings reveal a novel activity of

1,25-

> dihydroxyvitamin D3 and the VDR in regulation of primate innate

> immunity.

>

> PMID: 15985530 [PubMed - in process]