User talk:Adammichaelc

Vitamin D and Carsten Geisler[edit]

Hi. Concerning your recent contributions to T cell and related articles in which you state:

when Geisler references vitamin D levels, he is referring to calcidiol or 25 hydroxyvitamin D

and cite Geisler et al.,^[1] I believe your interpretation of what Geisler wrote it incorrect. From the abstract of the cited publication:

induction of PLC-γ1 was dependent on vitamin D and expression of the vitamin D receptor (VDR).

In the results section of the cited publication is written:

treatment with the active form of vitamin D (1,25-dihydroxyvitamin D3 (1,25(OH)₂D₃)) results in higher PLC-γ1 expression.

VDR is only activated by the active form of vitamin D (calcitriol) and not vitamin D itself. So when Geisler refers to vitamin D what he means is the activated form.

Also per WP:MEDMOS:

Do not hype a study by listing the names, credentials, institutions, or other "qualifications" of their authors.

Hence it is not generally appropriate to list the author of a study in the text, the author list in citation should sufficient.

Boghog (talk) 10:25, 26 December 2010 (UTC)[reply]

Hi,

I don't know how to respond to your comments as I'm new to Wikipedia editing.

There are basically 3 forms of vitamin D: cholecalciferol (vitamin D3), calcidiol (25-hydroxyvitamin D), and calcitriol (1,25-dihydroxyvitamin D3)

Cholecalciferol is ingested via supplementation or produced in the skin. Then it travels through the blood and is metabolized into calcidiol in the liver. Calcidiol is what Geitner referred to when he mentioned "circulating vitamin D levels" as it is the only reliable measure for adequate levels of vitamin D. When a doctor tests you for vitamin D sufficiency he tests your calcidiol or 25-hydroxyvitamin D.

Things get interesting at the next level. When there is sufficient circulating calcidiol, the body has activation centers throughout the body (we used to think the only activation center was in the kidneys) that can turn the pre-hormone calcidiol into the activated steroid hormone calcitriol. While it is true that only calcitriol can be utilized by the VDR, it is actually calcidiol (the pre-hormone), that you measure in the blood, since if there isn't enough calcidiol, calcitriol can't be produced where the need is.

For a good source on vitamin D physiology see the side column on page 3 of this NEJM piece by M Hollick: http://www.uth.tmc.edu/schools/med/imed/residency/chiefscorner/Documents/Articles/Endocrinology/holick.pdf

In the case of T-cells, Geitner's research shows that one of the activation centers is at the T-cell itself. The T-cell activates calcidiol and turns it into calcitriol. So yes, calcitriol is what directly binds to the VDR, but calcidiol levels are crucial, and even moving back a step we see that without adequate cholecalciferol intake (via sun or supplement), you won't have enough calcidiol, and thus you will also lack proper calcitriol levels near the VDR's throughout the body. Adam Chavez (talk) 22:10, 27 December 2010 (UTC)[reply]

Thanks for your reply and for the link to the NEJM article. I was under the impression that the hydroxylation of calcidiol to calcitriol is catalyzed by the CYP27B1 enzyme and CYP27B1 is only expressed in the kidneys. This is consistent with what is stated in the caption to figure 1 in the NEJM article. Do T-cells express CYP27B1 or a functionally equivalent enzyme? Boghog (talk) 22:30, 27 December 2010 (UTC)[reply]

OK, I now see after more thorough reading that reference #32 (Sigmundsdottir et al.) cited in the Geisler Nature Immunology paper shows that CYP27B1 is expressed by T cells and dendritic cells.^[2] Furthermore Geisler et al. show that ketoconazole, an inhibitor of CYP27B1 "inhibited VDR expression as well as PLC-γ1 induction". Sigmundsdottir in turn cites other work (references 33-35), that shows that keratinocytes and macrophages also possess CYP27B1 activity. Hence Geisler, et al. were not the first to demonstrate that T cells can activate vitamin D, but they did confirm it.

^ von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C (2010). "Vitamin D controls T cell antigen receptor signaling and activation of human T cells" (PDF). Nat. Immunol. 11 (4): 344–9. doi:10.1038/ni.1851. PMID 20208539. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, Butcher EC (2007). "DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27" (PDF). Nat. Immunol. 8 (3): 285–93. doi:10.1038/ni1433. PMID 17259988. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

Hi,

Thanks for your reply and the additional information. As a result of your message I am going to try to find all the cells that express CYP27B1; so far I have found that the kidney's, mammarian tissue, colon, epithelial tissue, T-cells and dendrites all express CYP27B1. I suspect there are more as I found the above from a quick search.

I will respond more thoroughly and re-write my T-cell edits with the Wiki etiquette you showed me above in mind when I get to a proper computer. I've been messaging you from my iPhone and it's quite a pain! Have a happy new year!

PS Do you use software to help quickly write out your sources? Or do you do it by hand?

Adam Chavez (talk) 18:56, 28 December 2010 (UTC)[reply]

That would be great if you find additional sources that document the tissue distribution of CYP27B1. If you do find additional data, I would be grateful if you would add it to the CYP27B1 article.

Concerning the immune system, vitamin D has a much broader effect than just priming T cells for activation. In general vitamin D seems to boost the innate immune system and dampen the adaptive immune system (see for example PMID 18212810, PMID 18854395, PMID 20119827, PMID 20221619, PMID 20427238).

Concerning citation formatting, please check out User:Diberri's Wikipedia template filling tool (instructions). Given a PubMed ID, one can quickly produce a full citation that can be copied and pasted into a Wikipedia article. If you want to include the citation "in-line", be sure that the "add ref tag" option of the template tool is turned on. If you want to include a reference in the further reading section, the "add ref tag" option should be left off.

Likewise, I wish you a happy new year! Cheers. Boghog (talk) 19:50, 28 December 2010 (UTC)[reply]

Great, thanks for the tool! PS I created a new discussion on the T-cell discussion page. It would be great to get your input so we can update the T-cell page with the latest understanding on vitamin D's role within the system. http://en.wikipedia.org/wiki/Talk:T_cell#T_Cells.2C_vitamin_D3_.28cholecalciferol.29.2C_calcidiol.2C_and_calcitriol Adam C (talk) 09:07, 3 January 2011 (UTC)[reply]

[pmid20208539-1] von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C (2010). "Vitamin D controls T cell antigen receptor signaling and activation of human T cells" (PDF). Nat. Immunol. 11 (4): 344–9. doi:10.1038/ni.1851. PMID 20208539. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[pmid17259988-2] Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, Butcher EC (2007). "DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27" (PDF). Nat. Immunol. 8 (3): 285–93. doi:10.1038/ni1433. PMID 17259988. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

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