Doxycycline inhibits TGF-b and reduces fibrosis

[StayPositive]

Abstract​

Purpose: It is well known that doxycycline has antibacterial and anti-inflammatory effects. In this study, we aimed to investigate the effects of doxycycline on the transforming growth factor (TGF) beta 1-induced matrix metalloproteinase (MMP) 2 expression, migration, and collagen contraction, and to determine its molecular mechanism on nasal polyp-derived fibroblasts (NPDF).

Methods: NPDFs were isolated from the nasal polyps of six patients. Doxycycline was used to pretreat TGF-beta-1-induced NPDFs and ex vivo organ cultures of nasal polyps. Cytotoxicity was evaluated by using a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. Smad2/3 is one of the major transcription factors of TGF-beta signaling. The expression levels of MMP2 and Smad2/3 were measured by using Western blotting, reverse transcription-polymerase chain reaction, and immunofluorescence staining. The enzymic activity of MMP2 was analyzed by using gelatin zymography. Fibroblast migration was evaluated by using transwell migration assays. Contractile activity was measured by a collagen gel contraction assay.

Results: The expression level of MMP2 in nasal polyp tissues increased in comparison with inferior turbinate tissues. TGF-beta-1-induced NPDFs were not affected by doxycycline (0-40 μg/mL). The expression levels of MMP2 and activation of Smad2/3 in TGF-beta-1-induced NPDFs and in organ cultures of nasal polyps were significantly downregulated with doxycycline pretreatment. Doxycycline also reduced TGF-beta-1-induced fibroblast migration and collagen contraction in NPDFs.

Conclusion: Doxycycline inhibited TGF-beta-1-induced MMP2 expression, migration, and collagen contraction via the Smad2/3 signal pathways in NPDFs.

Effect of doxycycline on transforming growth factor-beta-1-induced matrix metalloproteinase 2 expression, migration, and collagen contraction in nasal polyp-derived fibroblasts - PubMed

Doxycycline inhibited TGF-beta-1-induced MMP2 expression, migration, and collagen contraction via the Smad2/3 signal pathways in NPDFs.

pubmed.ncbi.nlm.nih.gov

 

[StayPositive]

There are others studies about that

Doxycycline Inhibits TGF-β1–Induced MMP-9 via Smad and MAPK Pathways in Human Corneal Epithelial Cells | IOVS | ARVO Journals

iovs.arvojournals.org

Effects of Doxycycline on Production of Growth Factors and Matrix Metalloproteinases in Pulmonary Fibrosis

Abstract. Background: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibrosis and a poor prognosis. Alveolar epithelial cells (AECs) are considered to play important roles by releasing growth factors and matrix metalloproteinases (MMPs) and by being involved in epithelial...

www.karger.com

 

[StayPositive]

We know TGF-b plays an important role in male pattern baldness. I think it would be smart to use it. But not in standard dosages (100mg-200mg per day) because it can alter the gut flora and can cause antibiotic resistance.

Doxycycline at low doses (<50 mg per day) does not exert antibacterial properties but only shows anti inflammatory effects without altering bacteria flora and without inducing antibiotic resistance.

Subantimicrobial-dose doxycycline in the treatment of moderate facial acne - PubMed

Subantimicrobial-dose doxycycline is an effective treatment for patients with moderate acne vulgaris.

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of doxycycline in the treatment of rosacea

Rosacea is a common, chronic, skin condition characterized by recurrent episodes of facial flushing, transient or persistent erythema, papules, pustules, and telangiectasias, in a symmetrical facial distribution. The etiology of rosacea remains unknown ...

www.ncbi.nlm.nih.gov

Clinical studies on the management of periodontal diseases utilizing subantimicrobial dose doxycycline (SDD)

Periodontitis, the most common chronic inflammatory condition known to mankind, is a disease that results in the destruction of tooth supporting tissu…

www.sciencedirect.com

Update on rosacea and anti-inflammatory-dose doxycycline - PubMed

Approximately 13 million individuals in the United Sates suffer from rosacea, a recurrent disease that may require long-term therapy. Topical and oral antibiotics have been used to treat rosacea; however, high-dose antibiotics or long-term, low-dose antibiotics commonly used for the treatment of...

pubmed.ncbi.nlm.nih.gov

http://www.ahdbonline.com/payer-perspectives-in-dermatology/1334-article-1334

There are tones of other studies on the subject (antibacterial/anti inflammatory dosage and effects of doxycycline) but i don't have the time to list all of them.

25mg per day seems a good dosage for anti inflammatory effect only. I am on it since 22 January. Rosacea reduced, cystic acne completely gone. For hair too soon to tell.

 

[Isneezedsohard]

We know TGF-b plays an important role in male pattern baldness. I think it would be smart to use it. But nit in standard dosages (100mg-200mg per day) which can alter the gut flora and cab cause antibiotic resistance.

Doxycycline at low doses (<50 mg per day) does not exert antibacterial properties but only shows anti inflammatory effects without altering bacteria flora and without inducing antibiotic resistance.

Safety and efficacy of doxycycline in the treatment of rosacea

Rosacea is a common, chronic, skin condition characterized by recurrent episodes of facial flushing, transient or persistent erythema, papules, pustules, and telangiectasias, in a symmetrical facial distribution. The etiology of rosacea remains unknown ...

www.ncbi.nlm.nih.gov

Clinical studies on the management of periodontal diseases utilizing subantimicrobial dose doxycycline (SDD)

Periodontitis, the most common chronic inflammatory condition known to mankind, is a disease that results in the destruction of tooth supporting tissu…

www.sciencedirect.com

Update on rosacea and anti-inflammatory-dose doxycycline - PubMed

Approximately 13 million individuals in the United Sates suffer from rosacea, a recurrent disease that may require long-term therapy. Topical and oral antibiotics have been used to treat rosacea; however, high-dose antibiotics or long-term, low-dose antibiotics commonly used for the treatment of...

pubmed.ncbi.nlm.nih.gov

Subantimicrobial-dose doxycycline in the treatment of moderate facial acne - PubMed

Subantimicrobial-dose doxycycline is an effective treatment for patients with moderate acne vulgaris.

pubmed.ncbi.nlm.nih.gov

http://www.ahdbonline.com/payer-perspectives-in-dermatology/1334-article-1334

Their are tones of other studies which talk about antibacterial/anti inflammatory dosage of doxycycline, but i don't have the time to list all of them.

25mg per day seems a good dosage for anti inflammatory effect only. I am on it since 22 January. Rosacea reduced, cystic acne completely gone. For hair too soon to tell.

R u still shedding? Ur protocol looks intense!

 

[StayPositive]

R u still shedding? Ur protocol looks intense!

I stared doxycycline at 25mg per day on 22 January for acne, and i just started Aspirin/Castor oil/ect today. So yeah i am still shedding

 

[StayPositive]

This study has shown that doxycycline can reduce inflammation even in the presence of DHT:

Abstract
Objectives: Investigation of osteoblastic responses to oxidative stress, induced by C-reactive protein (CRP) and IL-6 and ameliorating effects of doxycycline (Dox); using assays for 5-alpha dihydrotestosterone (DHT) as an antioxidant marker of healing. IL-6 and CRP are risk markers of periodontitis and prevalent comorbidities in periodontitis subjects.

Methods: Confluent monolayer cultures of osteoblasts were incubated with radiolabelled testosterone (14C-T) as substrate, in the presence or absence (Control) of pre-determined optimal concentrations of CRP, IL-6, Dox; alone and in combination (n=8) for 24h in MEM. The eluent was solvent-extracted for steroid metabolites. They were separated using TLC in a benzene/ acetone solvent system 4:1 v/v; and quantified using radioisotope scanning. The identity of formed metabolites was confirmed using the mobility of cold standards added to the samples and disclosed in iodine. Further confirmation of the authenticity of DHT was carried out by combined gas chromatrography-mass spectrometry, after derivatization to pentafluorobenzyloxime trimethyl silyl ether.

Results: The yields of DHT from 14C-testosterone showed 2-fold and 1.8-fold- inhibition in response to IL-6 and CRP respectively and 28% stimulation in response to Dox, via the 5-alpha reductase pathway. The combination of IL-6 + CRP showed a 2-fold reduction in the yields of DHT, elevated to control values when combined with Dox (n=8; p<0.001). Yields of 4-androstenedione showed an inverse relationship to those of DHT, in response to the agents tested, in keeping with the 17-beta hydroxysteroid dehydrogenase pathway.

Conclusions: Inhibition of DHT synthesis in osteoblasts by IL-6 and CRP was overcome by doxycycline. Oxidative actions of IL-6 and CRP; and antioxidant actions of Dox are reinforced by the metabolic yields of DHT in response to agents tested. Using a novel metabolically active model allows closer extrapolation to in vivo conditions; in the context of adjunctive therapeutic applications for periodontitis and prevalent comorbidities.

Antioxidant response of osteoblasts to doxycycline in an inflammatory model induced by C-reactive protein and interleukin-6 - PubMed

Inhibition of DHT synthesis in osteoblasts by IL-6 and CRP was overcome by doxycycline. Oxidative actions of IL-6 and CRP; and antioxidant actions of Dox are reinforced by the metabolic yields of DHT in response to agents tested. Using a novel metabolically active model allows closer...

pubmed.ncbi.nlm.nih.gov

 

[StayPositive]

It seems that doxycycline increases pge2 and decreases TNF-alpha

Abstract​

Purpose: We explored the anti-inflammatory effects of doxycycline in experimental uveitis and the underlying mechanisms.

Methods: Rats with endotoxin-induced uveitis (EIU) received doxycycline (1.5 mg/kg) or the control vehicle via intraperitoneal injection. Clinical scores were graded under a slit lamp. Rat peritoneal macrophages were used in vitro to further explore the anti-inflammatory mechanisms of doxycycline. The levels of nitric oxide (NO), TNF-α, IL-1β, prostaglandin E2 (PGE2), cyclooxygenase (COX)-2, I kappa B-α (IκB-α), inducible nitric oxide synthase (iNOS), Akt, caspase-3, and nuclear factor-kappa B (NF-κB) were analyzed.

Results: Treatment with doxycycline dramatically reduced the clinical scores of EIU (P < 0.001), with significant decreases in inflammatory cell infiltration, protein concentrations, and the production of NO, TNF-α, and IL-1β in the aqueous humor (AqH). In vitro, doxycycline significantly inhibited the production of NO, IL-1β, and TNF-α in peritoneal macrophages by modulating the PI3K/Akt/IκB-α/NF-κB pathway. Importantly, we found that doxycycline significantly enhanced COX2 expression and PGE2 production both in vivo and in vitro. More importantly, blockade of the EP4 receptor of PGE2 significantly reversed the doxycycline-mediated inhibition of macrophages and the PI3K/Akt pathway in vitro. Furthermore, simultaneous injection of an EP4 antagonist and doxycycline significantly blocked the doxycycline-mediated attenuation of EIU.

Conclusions: Doxycycline can ameliorate EIU, and PGE2-EP4 signaling is essential for the anti-inflammatory effects of doxycycline in vitro and in vivo.

Doxycycline Attenuates Endotoxin-Induced Uveitis by Prostaglandin E2-EP4 Signaling - PubMed

Doxycycline can ameliorate EIU, and PGE2-EP4 signaling is essential for the anti-inflammatory effects of doxycycline in vitro and in vivo.

pubmed.ncbi.nlm.nih.gov

 

[StayPositive]

Another study about doxycycline effects on pge2

Tetracycline up-regulates COX-2 expression and prostaglandin E2 production independent of its effect on nitric oxide - PubMed

Tetracyclines (doxycycline and minocycline) augmented (one- to twofold) the PGE2 production in human osteoarthritis-affected cartilage (in the presence or absence of cytokines and endotoxin) in ex vivo conditions. Similarly, bovine chondrocytes stimulated with LPS showed (one- to fivefold) an...

pubmed.ncbi.nlm.nih.gov

 

[Isneezedsohard]

Another study about doxycycline effects on pge2

Tetracycline up-regulates COX-2 expression and prostaglandin E2 production independent of its effect on nitric oxide - PubMed

Tetracyclines (doxycycline and minocycline) augmented (one- to twofold) the PGE2 production in human osteoarthritis-affected cartilage (in the presence or absence of cytokines and endotoxin) in ex vivo conditions. Similarly, bovine chondrocytes stimulated with LPS showed (one- to fivefold) an...

pubmed.ncbi.nlm.nih.gov

What’s the downside to crushing PGE2

 

[StayPositive]

What’s the downside to crushing PGE2

Since PGE2 is very beneficial for hair growth, crushing it will have a negative impact on hair. Doxycycline likely increases pge2.

 

[Isneezedsohard]

Since PGE2 is very beneficial for hair growth, crushing it will have a negative impact on hair. Doxycycline increases pge2.

I meant PGD2; my mistake!

 

[StayPositive]

I meant PGD2; my mistake!

I think crushing PGD2 while maintaining high or normal levels of PGE2 means no further hair loss

 

[HairOnFire]

Funny you should mention this. I recall that about 25 years ago there was a doctor at the Mayo Clinic who used oral minocycline in his practice to treat pattern baldness, and claimed that it could halt hair loss in the majority of Androgenetic Alopecia cases. Minocycline is from the same class of drug as doxycycline (the tetracyclines), and shares many of it's properties. One advantage that minocycline has over doxycycline is that its more lipid soluble, and thus would theoretically penetrate the hair follicle better (note: both minocycline and doxycycline are lipid soluble, but minocycline is superior in this regard). Of course, minocycline and doxycycline both have a number of side-effects.

MMPs are a prime candidate as to why minocycline/doxycycline could affect hair growth.

 

[TurboFixer]

Funny you should mention this. I recall that about 25 years ago there was a doctor at the Mayo Clinic who used oral minocycline in his practice to treat pattern baldness, and claimed that it could halt hair loss in the majority of Androgenetic Alopecia cases. Minocycline is from the same class of drug as doxycycline (the tetracyclines), and shares many of it's properties. One advantage that minocycline has over doxycycline is that its more lipid soluble, and thus would theoretically penetrate the hair follicle better (note: both minocycline and doxycycline are lipid soluble, but minocycline is superior in this regard). Of course, minocycline and doxycycline both have a number of side-effects.

MMPs are a prime candidate as to why minocycline/doxycycline could affect hair growth.

25 years ago? so why didn't it catch on?

if it were super effective wouldn't we all know by now?

 

[Frenchboy]

Funny, i’m having 100mg/day (for acné, not a serious case)

I don’t know if it affect my hairloss, but good to know!

 

[Gegen]

Funny, i’m having 100mg/day (for acné, not a serious case)

I don’t know if it affect my hairloss, but good to know!

"acné" French spotted lol.

 

[Gegen]

Some really interesting new things being posted on the forum recently.

Yeah, we can especially thank FollicleGuardian who created 4 threads in a matter of 2-3 days. He really is the personal guard of our hair.

 

[StayPositive]

25 years ago? so why didn't it catch on?

if it were super effective wouldn't we all know by now?

It's probably not super effective

Just another weapon we can add in our arsenal

 

[HairOnFire]

25 years ago? so why didn't it catch on?

if it were super effective wouldn't we all know by now?

A couple of reasons why it would fly under the radar:

- It doesn't directly stimulate hair growth.
- Antibiotics like minocycline are usually prescribed for a week or two, then stopped, which is obviously not enough time to impact Androgenetic Alopecia.
- Minocycline is sometimes given for longer periods - 3 or 4 months for acne, for example - but that's still not a long time, and most people who have acne don't have Androgenetic Alopecia at the same time, simply because they are too young (acne is most prominent in teenagers, before baldness even comes into the picture).

If minocycline has an effect on Androgenetic Alopecia, it would probably be for slowing down the Androgenetic Alopecia process, rather than re-growing hair. Which implies that it would not be terribly useful for guys who already have significant hair loss. It's something you'd use early on, to try and prevent scalp hair follicles from miniaturizing.

 

[StayPositive]

What if someone gets sick and anti-biotics no longer work cause they were used on hair?

You obviously didn't read the studies i posted on doxycycline's subantimicrobial dosages.