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Innate immunity activation of sebocyte cells by living bacteria. Evidence of apotential immunosuppressive effect of DHT
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Innate immunity activation of sebocyte cells by living bacteria. Evidence of apotential immunosuppressive effect of DHT
INTRODUCTION & HYPOTHESIS
Acne is a common skin pathology targeting the pilosebaceous unit, characterized by sebum hypersecretion together with bacterial infection and inflammation. Clinically speaking, the process is clearly under the dependence of an androgenic stimulation. We previously established and characterized an androgen-sensitive human sebocyte cell line (SEBO662AR) and showed that dihydrotestosterone (DHT) induced the lipogenic differentiation of these cells (1). Here we investigated the innate immunity activation of sebocytes by living bacteria. Staphylococcus aureus, Staphylococcus epidermidis, Cutibacterium acnes (formerly Propionibacterium acnes) and Pseudomonas aeruginosa were selected for their relevance in skin physiopathology. Focusing on C. acnes, we also looked at the effects of DHT on this immune response, as well as the effects of both on the lipid accumulation in this cell model.
Skin bacteria differentially stimulate innate immunity activation of sebocytes as it is the case for other skin cells. We hypothesized an effect of active androgens (DHT) on the response of androgen-sensitive sebocyte cells to bacteria, in terms of modulation of innate immunity response and lipid production.
MATERIALS & MEHODS
S. aureus (ATCC 29213), S. epidermidis (CCM 2124) and P. aeruginosa (PAK strain) were grown on Muller Hinton agar plates and incubated for 24 h at 37°C. C. acnes (ATCC 4919) were grown on Muller Hinton blood agar plates and incubated for 48 h at 37°C under anaerobic conditions. Keratinocytes were infected at a multiplicity of infection (MOI) of 1 with P. aeruginosa or 10 with the other bacterial species and incubated for 6 h (transcriptomic analyzes) and 24 h (ELISA assays) at 37°C in 5 % CO2. RT-q-PCR and ELISA assays were previously described2. Immunofluorescence and lipid accumulation assay with the fluorescent probe Bodipy were performed as in 1.
CONCLUSIONS
In this model,
– Bacteria differentially induce the overexpression of CXC chemokines, CCL20 and the pro-inflammatory cytokine IL-6. It is also the case for antibacterial peptide transcripts S100A7 and β-defensin 2 (BD2), but with an apparent different selectivity.
– DHT treatment decreases the expression of the chemokines and IL-6 both at the mRNA and protein level and can be regarded as an “innate immunosuppressor”.
– We expect a different mechanism for antibacterial peptides overexpression, on which we observed no significant effect of DHT.
– Finally, bacteria (C. acnes) potentialized the DHT-induced accumulation of lipid droplets in SEBO662AR cells.
– These experimental data could be regarded as preliminary elements suggesting a possible cooperation between infection and androgens in sebaceous disorders.
https://www.bioalternatives.com/en/immunity-activation-of-sebocytes-bacteria-immunosuppressive-effect-dht/
Acne is a common skin pathology targeting the pilosebaceous unit, characterized by sebum hypersecretion together with bacterial infection and inflammation. Clinically speaking, the process is clearly under the dependence of an androgenic stimulation. We previously established and characterized an androgen-sensitive human sebocyte cell line (SEBO662AR) and showed that dihydrotestosterone (DHT) induced the lipogenic differentiation of these cells (1). Here we investigated the innate immunity activation of sebocytes by living bacteria. Staphylococcus aureus, Staphylococcus epidermidis, Cutibacterium acnes (formerly Propionibacterium acnes) and Pseudomonas aeruginosa were selected for their relevance in skin physiopathology. Focusing on C. acnes, we also looked at the effects of DHT on this immune response, as well as the effects of both on the lipid accumulation in this cell model.
Skin bacteria differentially stimulate innate immunity activation of sebocytes as it is the case for other skin cells. We hypothesized an effect of active androgens (DHT) on the response of androgen-sensitive sebocyte cells to bacteria, in terms of modulation of innate immunity response and lipid production.
MATERIALS & MEHODS
S. aureus (ATCC 29213), S. epidermidis (CCM 2124) and P. aeruginosa (PAK strain) were grown on Muller Hinton agar plates and incubated for 24 h at 37°C. C. acnes (ATCC 4919) were grown on Muller Hinton blood agar plates and incubated for 48 h at 37°C under anaerobic conditions. Keratinocytes were infected at a multiplicity of infection (MOI) of 1 with P. aeruginosa or 10 with the other bacterial species and incubated for 6 h (transcriptomic analyzes) and 24 h (ELISA assays) at 37°C in 5 % CO2. RT-q-PCR and ELISA assays were previously described2. Immunofluorescence and lipid accumulation assay with the fluorescent probe Bodipy were performed as in 1.
CONCLUSIONS
In this model,
– Bacteria differentially induce the overexpression of CXC chemokines, CCL20 and the pro-inflammatory cytokine IL-6. It is also the case for antibacterial peptide transcripts S100A7 and β-defensin 2 (BD2), but with an apparent different selectivity.
– DHT treatment decreases the expression of the chemokines and IL-6 both at the mRNA and protein level and can be regarded as an “innate immunosuppressor”.
– We expect a different mechanism for antibacterial peptides overexpression, on which we observed no significant effect of DHT.
– Finally, bacteria (C. acnes) potentialized the DHT-induced accumulation of lipid droplets in SEBO662AR cells.
– These experimental data could be regarded as preliminary elements suggesting a possible cooperation between infection and androgens in sebaceous disorders.
https://www.bioalternatives.com/en/immunity-activation-of-sebocytes-bacteria-immunosuppressive-effect-dht/
Cat with a Hat- Posts : 75
Join date : 2019-08-19
Re: Innate immunity activation of sebocyte cells by living bacteria. Evidence of apotential immunosuppressive effect of DHT
Androgens have been generally accepted as immune suppressing. One example of this is the fact that asthma (a hypersensitive immune response) is more prevalent in males as children, but the reverse is true for adults. Once the boys hit adolescence, their androgens reduce the prevalence of asthma.
NDW- Posts : 216
Join date : 2011-06-18
Re: Innate immunity activation of sebocyte cells by living bacteria. Evidence of apotential immunosuppressive effect of DHT
NDW wrote:Androgens have been generally accepted as immune suppressing. One example of this is the fact that asthma (a hypersensitive immune response) is more prevalent in males as children, but the reverse is true for adults. Once the boys hit adolescence, their androgens reduce the prevalence of asthma.
I remember reading that Estrogens also reduce IL-6 and Lipoprotein a, but I wonder how much that is due to an immune suppression vs curing a problem at its core. As for the study above, wouldn't the info mean that such suppression would allow for pathogens to multiply and cause damage?
Cat with a Hat- Posts : 75
Join date : 2019-08-19
Re: Innate immunity activation of sebocyte cells by living bacteria. Evidence of apotential immunosuppressive effect of DHT
I'm not sure what your first sentence is saying, but it has been established that males are more susceptible to infectious diseases and females are more susceptible to auto-immune diseases.
NDW- Posts : 216
Join date : 2011-06-18
Re: Innate immunity activation of sebocyte cells by living bacteria. Evidence of apotential immunosuppressive effect of DHT
NDW wrote:I'm not sure what your first sentence is saying, but it has been established that males are more susceptible to infectious diseases and females are more susceptible to auto-immune diseases.
Yeah sorry, what I meant to say was wether estrogen reducing lipoprotein a is done by, for example, increaseing its breakdown/excretion, or is it actually reducing the need for it. As far as suseptabilities in genders, I was never aware. Interesting to note, I am a male, but more extrogenic, and it does seem that my hairloss also includes "resistant areas".
Cat with a Hat- Posts : 75
Join date : 2019-08-19
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