A novel control of human keratin expression: cannabinoid receptor 1-mediated signaling down-regulates the expression of keratins K6 and K16 in human keratinocytes in vitro and in situ

PeerJ. 2013 Feb 19;1:e40. doi: 10.7717/peerj.40. Print 2013.
A novel control of human keratin expression: cannabinoid receptor 1-mediated signaling down-regulates the expression of keratins K6 and K16 in human keratinocytes in vitro and in situ.
Ramot Y, Sugawara K, Zákány N, Tóth BI, Bíró T, Paus R.

Department of Dermatology, University of Luebeck , Luebeck , Germany ; Department of Dermatology, Hadassah-Hebrew University Medical Center , Jerusalem , Israel.

Cannabinoid receptors (CB) are expressed throughout human skin epithelium. CB1 activation inhibits human hair growth and decreases proliferation of epidermal keratinocytes. Since psoriasis is a chronic hyperproliferative, inflammatory skin disease, it is conceivable that the therapeutic modulation of CB signaling, which can inhibit both proliferation and inflammation, could win a place in future psoriasis management. Given that psoriasis is characterized by up-regulation of keratins K6 and K16, we have investigated whether CB1 stimulation modulates their expression in human epidermis. Treatment of organ-cultured human skin with the CB1-specific agonist, arachidonoyl-chloro-ethanolamide (ACEA), decreased K6 and K16 staining intensity in situ. At the gene and protein levels, ACEA also decreased K6 expression of cultured HaCaT keratinocytes, which show some similarities to psoriatic keratinocytes. These effects were partly antagonized by the CB1-specific antagonist, AM251. While CB1-mediated signaling also significantly inhibited human epidermal keratinocyte proliferation in situ, as shown by K6/Ki-67-double immunofluorescence, the inhibitory effect of ACEA on K6 expression in situ was independent of its anti-proliferative effect. Given recent appreciation of the role of K6 as a functionally important protein that regulates epithelial wound healing in mice, it is conceivable that the novel CB1-mediated regulation of keratin 6/16 revealed here also is relevant to wound healing. Taken together, our results suggest that cannabinoids and their receptors constitute a novel, clinically relevant control element of human K6 and K16 expression.

CausticSymmetry wrote:PeerJ. 2013 Feb 19;1:e40. doi: 10.7717/peerj.40. Print 2013.
A novel control of human keratin expression: cannabinoid receptor 1-mediated signaling down-regulates the expression of keratins K6 and K16 in human keratinocytes in vitro and in situ.
Ramot Y, Sugawara K, Zákány N, Tóth BI, Bíró T, Paus R.

Department of Dermatology, University of Luebeck , Luebeck , Germany ; Department of Dermatology, Hadassah-Hebrew University Medical Center , Jerusalem , Israel.

Cannabinoid receptors (CB) are expressed throughout human skin epithelium. CB1 activation inhibits human hair growth and decreases proliferation of epidermal keratinocytes. Since psoriasis is a chronic hyperproliferative, inflammatory skin disease, it is conceivable that the therapeutic modulation of CB signaling, which can inhibit both proliferation and inflammation, could win a place in future psoriasis management. Given that psoriasis is characterized by up-regulation of keratins K6 and K16, we have investigated whether CB1 stimulation modulates their expression in human epidermis. Treatment of organ-cultured human skin with the CB1-specific agonist, arachidonoyl-chloro-ethanolamide (ACEA), decreased K6 and K16 staining intensity in situ. At the gene and protein levels, ACEA also decreased K6 expression of cultured HaCaT keratinocytes, which show some similarities to psoriatic keratinocytes. These effects were partly antagonized by the CB1-specific antagonist, AM251. While CB1-mediated signaling also significantly inhibited human epidermal keratinocyte proliferation in situ, as shown by K6/Ki-67-double immunofluorescence, the inhibitory effect of ACEA on K6 expression in situ was independent of its anti-proliferative effect. Given recent appreciation of the role of K6 as a functionally important protein that regulates epithelial wound healing in mice, it is conceivable that the novel CB1-mediated regulation of keratin 6/16 revealed here also is relevant to wound healing. Taken together, our results suggest that cannabinoids and their receptors constitute a novel, clinically relevant control element of human K6 and K16 expression.

eccg activates cb1 receptor, maybe this is why a i read a few accounts of hair loss while on it, tho it decreases other things associated with hair loss.

http://ip.com/patfam/en/42248108

cinnamon blocks cb1 receptor
http://ip.com/patfam/en/42248108

Thanks for this information, CS.

This is one more piece of evidence why cannabinoids are good for auto-immune conditions.

I know a couple of people here were experimenting with the cannabis oil. I'd like to know how that went. But in the meantime, I'll continue to try to upregulate the CB1 receptor   .

AS54 wrote:Thanks for this information, CS.

This is one more piece of evidence why cannabinoids are good for auto-immune conditions.

I know a couple of people here were experimenting with the cannabis oil. I'd like to know how that went. But in the meantime, I'll continue to try to upregulate the CB1 receptor   .

"CB1 activation inhibits human hair growth and decreases proliferation of epidermal keratinocytes."

Wouldn't we want to downregulate the receptor?

CF,

Yes, should have qualified that. I was referring to auto-immune skin conditions. And other things like keratosis pilaris. Given this is a hair forum, I should have made that clear. Apologies.

I mean to say that I will use this for KP, and some psoriasis.

When it comes to hair, I'm not really that sure on the magnitude of effect things like marijuana or cannabis oil would have on hair. Its one of many signalling chains involved in hair growth. It would be interesting to know just how big a role this receptor plays though, no doubt. But for me personally, I've seen big improvements in skin, particularly with the KP, so that's what I was referring to.

When it comes to the the biochemical stuff, we can't always look at it as an issue of "Okay, this plant contains a chemical that activates this receptor. That means it will lead to hairloss." Because I have to guess we could also find pro-hair chemicals and phytoestrogens present in the same plant. Who wins the tug of war, know what I mean?

AS54, thanks for the reply.

Yaer, thanks for the information about cinnamon.

CS, what would be your thoughts on a cinnamon supplement?  Would you say it would most likely be neutral to pro-hair?

CF wrote:AS54, thanks for the reply.

Yaer, thanks for the information about cinnamon.

CS, what would be your thoughts on a cinnamon supplement?  Would you say it would most likely be neutral to pro-hair?

I've tried cinnamon in the past. I did not notice anything unusual. I took it internally. There are topical formulations, and I've never tried them.

In past I made mention of this study regarding both curcumin and trans-resveratrol - These polyphenols also reduce body weight in mice similar to that produced by a CB1 antagonist/inverse agonist

http://jpet.aspetjournals.org/content/330/1/31.long

Thanks, CS.