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Brazilian Journal of Medical and... 2020Acne is a kind of common, chronic skin condition caused by the inflammation of the sebaceous glands in hair follicles. Recent studies have demonstrated that baicalin...
Acne is a kind of common, chronic skin condition caused by the inflammation of the sebaceous glands in hair follicles. Recent studies have demonstrated that baicalin (BA) possesses potential anti-inflammatory properties. In this study, we evaluated the anti-inflammatory activity of BA in vitro and in vivo. Heat-killed Propionibacterium acnes-induced THP-1 cells and live P. acnes-injected male Sprague Dawley rats were used for establishing the acne model. The rate of ear swelling was calculated, and the severity was determined by hematoxylin and eosin staining. The production of cytokines [interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF-α)] in the cell supernatant and ear tissue homogenates was measured by ELISA. Protein levels of JNK, ERK, P38, IκBα, P65, Nod-like receptor pyrin domain-containing 3 (NLRP3), pro-caspase-1, and IL-1β in THP-1 cells and ear tissues were detected by western blotting. NLRP3 and IL-1β were detected by immunohistochemistry, and the NLRP3, IL-1β and pro-caspase-1 mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that BA decreased the expression of pro-inflammatory cytokines in vitro and in vivo. Moreover, BA down-regulated the phosphorylation of JNK, ERK1/2, and κBα and inhibited the nuclear translocation of p65. Furthermore, BA inhibited the activation of NLRP3 inflammasome, at both the gene and protein levels. Taken together, the results demonstrated that BA might exert its anti-inflammatory activity by inhibiting NF-κB/MAPK signaling pathways and consequently suppressing the activation of the NLRP3 inflammasome both in vivo and in vitro.
Topics: Animals; Dermatitis; Flavonoids; Inflammasomes; Inflammation; Interleukin-1beta; MAP Kinase Signaling System; Male; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Propionibacterium acnes; Rats; Rats, Sprague-Dawley; Signal Transduction
PubMed: 33111746
DOI: 10.1590/1414-431X20209949 -
Indian Journal of Dermatology,... 2017Acne, the most common skin disease, is a disorder of pilosebaceous units that affects adolescents mainly and adults occasionally. The pathogenesis is multifactorial.... (Review)
Review
Acne, the most common skin disease, is a disorder of pilosebaceous units that affects adolescents mainly and adults occasionally. The pathogenesis is multifactorial. Besides genetic predisposition, other major factors include the action of androgens, pro-inflammatory lipids acting as ligands of peroxisome proliferator-activated receptors in the sebocytes, toll-like receptor-2 acting on keratinocytes, recognition of pathogen-associated molecular patterns, cytokines, chemokines, inflammasomes, neuroendocrine regulatory mechanisms, diet and other pro-inflammatory targets implicated in the activation of immune detection and response. Most of these factors converge on mammalian target of rapamycin complex1 (mTORC1) activation which is further enhanced by the nutrient signaling of Western diet. This multitude of pathogenic factors has led to a new armamentarium of drugs for the treatment of acne. Topical anti-androgens, insulin-like growth factor-1 inhibitors, peroxisome proliferator-activated receptor-modulators, acetylcholine inhibitors, topical retinoic acid metabolism-blocking agents, vitamin D analogues, antimicrobial peptides, interleukin-1α and interleukin-1β blockers and immunotherapy are some of the novel treatment options.
Topics: Acne Vulgaris; Administration, Topical; Dermatologic Agents; Humans; Inflammation Mediators; Peroxisome Proliferator-Activated Receptors; Propionibacterium acnes; Sebaceous Glands; TOR Serine-Threonine Kinases; Treatment Outcome
PubMed: 28195079
DOI: 10.4103/0378-6323.199581 -
Acta Dermato-venereologica Sep 2014Increasing antibiotic resistance in the population of Propionibacterium acnes is a major concern. Our aims were to examine the clonal relationships and anatomical...
Increasing antibiotic resistance in the population of Propionibacterium acnes is a major concern. Our aims were to examine the clonal relationships and anatomical distribution of resistant and sensitive P. acnes. A collection of 350 P. acnes isolates was therefore used to determine the minimum inhibitory concentration of tetracycline, erythro-mycin and clindamycin, multilocus sequence type, and the identity of genetic resistance markers. Two hitherto unknown resistance mutations were detected. Resistant P. acnes mainly belonged to clonal clusters in division I-1a frequently isolated from skin and associated with moderate to severe acne. All high-level tetracycline resistant strains were members of a single clone. Multiple isolates from distinct anatomic areas of surface skin and follicles of 2 acne patients revealed substantial clonal diversity between areas and co-existence of resistant and sensitive clones. Fifty-two percent of Danish acne patients and 43% of controls carried at least one resistant P. acnes strain, resistance to clindamycin being most frequent followed by tetracycline and erythromycin. Resistance to tetracycline was detected exclusively among isolates from acne patients. In conclusion, antibiotic resistance is associated with particular evolutionary clades of P. acnes and a substantial part is due to a single geographically widespread clone (ST3). Individuals carry a strikingly complex population of P. acnes with distinct virulence potential and antibiotic resistance.
Topics: Acne Vulgaris; Anti-Bacterial Agents; Case-Control Studies; Denmark; Drug Resistance, Multiple, Bacterial; Gram-Positive Bacterial Infections; Humans; Propionibacterium acnes
PubMed: 24577497
DOI: 10.2340/00015555-1794 -
British Journal of Pharmacology Jul 2019Propionibacterium acnes is a Gram-positive bacterium associated with the skin disorder acne. In this study, as fatty acids are considered to be important in the life...
BACKGROUND AND PURPOSE
Propionibacterium acnes is a Gram-positive bacterium associated with the skin disorder acne. In this study, as fatty acids are considered to be important in the life habitat of P. acnes, we tested our lipopeptide library in an attempt to create potent P. acnes-specific antimicrobial agents.
EXPERIMENTAL APPROACH
The antimicrobial activity of various lipopeptides was determined by measuring their minimal inhibitory concentration (MIC). Lipids from P. acnes were used to explore their mode of action. RAW264.7 cells stimulated with LPS and P. acnes respectively were used to measure their anti-inflammatory activity. Mice ears injected with P. acnes were used to assess the antimicrobial and anti-inflammatory effects of the peptides tested in vivo.
KEY RESULTS
The most potent candidate, C16-KWKW, was observed to be more active against P. acnes than against other non-targeted bacterial strains, such as Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The mode of action of C16-KWKW was observed to be through interference with the integrity of the bacterial membrane, thereby impairing membrane permeability and causing leakage of inner contents of bacterial cells. Furthermore, C16-KWKW inhibited the expression of pro-inflammatory cytokines, such as IL-1β, TNF-α, and inducible NOS stimulated by both LPS and P. acnes, thus showing potential anti-inflammatory activity, which was further verified in the in vivo animal studies.
CONCLUSIONS AND IMPLICATIONS
C16-KWKW is a lipopeptide displaying both anti-P. acnes and anti-inflammatory effects in vitro and in vivo and shows potential as a treatment for acne vulgaris induced by P. acnes.
Topics: Acne Vulgaris; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Cell Line; Cyclooxygenase 2; Female; Humans; Interleukin-1beta; Lipopeptides; Mice; Microbial Sensitivity Tests; NF-kappa B; Nitric Oxide Synthase Type II; Propionibacterium acnes; Tumor Necrosis Factor-alpha
PubMed: 30927447
DOI: 10.1111/bph.14680 -
The Journal of Investigative Dermatology Sep 2009In this issue, Iinuma et al. show that Propionibacterium acnes (P. acnes)-conditioned medium and formalin-killed P. acnes augment intracellular lipid formation in...
In this issue, Iinuma et al. show that Propionibacterium acnes (P. acnes)-conditioned medium and formalin-killed P. acnes augment intracellular lipid formation in hamster sebocytes by increasing the de novo synthesis of triacylglycerols. This commentary summarizes the current knowledge of the association of P. acnes with sebaceous lipogenesis, inflammation, and innate immunity, and points out the concurrent evidence that P. acnes-induced lipids may represent a recruitment of allies and/or enemies of the human skin.
Topics: Acne Vulgaris; Animals; Corticotropin-Releasing Hormone; Cricetinae; DNA-Binding Proteins; Immunity, Innate; Inflammation; Lipogenesis; Liver X Receptors; Orphan Nuclear Receptors; Propionibacterium acnes; Receptors, Cytoplasmic and Nuclear; Sebaceous Glands; Toll-Like Receptor 2
PubMed: 19809423
DOI: 10.1038/jid.2009.190 -
MBio 2012Investigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle...
UNLABELLED
Investigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne.
IMPORTANCE
Propionibacterium acnes is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11 P. acnes phages, thereby substantially increasing the amount of available genomic information about this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages, P. acnes phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of P. acnes; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne.
Topics: Bacteriolysis; Bacteriophages; Base Composition; DNA, Viral; Genes, Viral; Genetic Variation; Genome, Viral; Host Specificity; Humans; Molecular Sequence Data; Propionibacterium acnes; Sebaceous Glands; Sequence Analysis, DNA; Sequence Homology, Nucleic Acid; Skin; Synteny
PubMed: 23015740
DOI: 10.1128/mBio.00279-12 -
Journal of Microbiology and... Jun 2018(CC) is widely used in Asian countries to treat inflammatory diseases. We investigated the anti-inflammatory activity of the aqueous fraction separated from CC extract...
(CC) is widely used in Asian countries to treat inflammatory diseases. We investigated the anti-inflammatory activity of the aqueous fraction separated from CC extract and of berberine, its key bioactive component, in human keratinocytes and the possible molecular mechanisms underlying this. Treating HaCaT keratinocytic cells with heat-killed induced nitric oxide and proinflammatory cytokine (, tumor necrosis factor-α, interleukin (IL)-1β, and IL-8) production and their mRNA expression; these effects were suppressed by pretreatment with the aqueous fraction or berberine, which also suppressed the phosphorylation of ERK, JNK, and p38 kinases and the nuclear expression of nuclear factor (NF)-κB p65 in -stimulated cells. Thus, the aqueous fraction and berberine effectively exerted anti-inflammatory activities by suppressing mitogen-activated protein kinase and NF-κB signaling pathways in human keratinocytes and may be used for treating -induced inflammatory skin diseases.
Topics: Anti-Inflammatory Agents; Berberine; Cell Line; Coptis; Gene Expression Profiling; Humans; Immunologic Factors; Inflammation; Keratinocytes; Nitric Oxide; Plant Extracts; Propionibacterium acnes
PubMed: 29642289
DOI: 10.4014/jmb.1712.12051 -
PloS One Apr 2011In the progression of acne vulgaris, the disruption of follicular epithelia by an over-growth of Propionibacterium acnes (P. acnes) permits the bacteria to spread and...
BACKGROUND
In the progression of acne vulgaris, the disruption of follicular epithelia by an over-growth of Propionibacterium acnes (P. acnes) permits the bacteria to spread and become in contact with various skin and immune cells.
METHODOLOGY/PRINCIPAL FINDINGS
We have demonstrated in the present study that the Christie, Atkins, Munch-Peterson (CAMP) factor of P. acnes is a secretory protein with co-hemolytic activity with sphingomyelinase that can confer cytotoxicity to HaCaT keratinocytes and RAW264.7 macrophages. The CAMP factor from bacteria and acid sphingomyelinase (ASMase) from the host cells were simultaneously present in the culture supernatant only when the cells were co-cultured with P. acnes. Either anti-CAMP factor serum or desipramine, a selective ASMase inhibitor, significantly abrogated the P. acnes-induced cell death of HaCaT and RAW264.7 cells. Intradermal injection of ICR mouse ears with live P. acnes induced considerable ear inflammation, macrophage infiltration, and an increase in cellular soluble ASMase. Suppression of ASMase by systemic treatment with desipramine significantly reduced inflammatory reaction induced by intradermal injection with P. acnes, suggesting the contribution of host ASMase in P. acnes-induced inflammatory reaction in vivo. Vaccination of mice with CAMP factor elicited a protective immunity against P. acnes-induced ear inflammation, indicating the involvement of CAMP factor in P. acnes-induced inflammation. Most notably, suppression of both bacterial CAMP factor and host ASMase using vaccination and specific antibody injection, respectively, cooperatively alleviated P. acnes-induced inflammation.
CONCLUSIONS/SIGNIFICANCE
These findings envision a novel infectious mechanism by which P. acnes CAMP factor may hijack host ASMase to amplify bacterial virulence to degrade and invade host cells. This work has identified both CAMP factor and ASMase as potential molecular targets for the development of drugs and vaccines against acne vulgaris.
Topics: Acne Vulgaris; Animals; Bacterial Proteins; Cell Line; Dermatologic Agents; Desipramine; Humans; Mice; Mice, Inbred CBA; Propionibacterium acnes; Sphingomyelin Phosphodiesterase; Virulence
PubMed: 21533261
DOI: 10.1371/journal.pone.0014797 -
Scientific Reports Feb 2016We present a species-wide comparative analysis of 90 genomes of Propionibacterium acnes that represent the known diversity of the species. Our results are augmented by...
We present a species-wide comparative analysis of 90 genomes of Propionibacterium acnes that represent the known diversity of the species. Our results are augmented by six high-quality genomes and a manual investigation of all gene-sized indels found in the strains. Overall, the order of genes is conserved throughout the species. A public sybil database for easy comparative analysis of the 90 genomes was established. The analysis of indels revealed a total of 66 loci of non-core genes that correlate with phylogenetic clades. No gene was strain-specific in agreement with our conclusion that the P. acnes pan-genome is closed. An exhaustive search for homopolymeric tracts (HPTs) identified a total of 54 variable-length HPTs almost exclusively of guanine/cytosines located between genes or affecting the reading frame of genes. The repeat variation was consistent with phylogenetic clades suggesting slow accumulation over time rather than active modification. By transcriptome analysis we demonstrate how an HPT variation can affect the gene expression levels. Selected cases of both indels and HPTs are described. The catalogued data and the public P. acnes Sybil database provide a solid foundation for generating hypotheses and facilitate comparative genetic analyses in future P. acnes research.
Topics: Databases, Nucleic Acid; Genome, Bacterial; Genomic Instability; INDEL Mutation; Propionibacterium acnes
PubMed: 26857276
DOI: 10.1038/srep20662 -
Microbes and Infection Jul 2006Acne is a common skin disorder of the pilosebaceous unit. In addition to genetic, hormonal and environmental factors, abnormal colonization by Propionibacterium acnes...
Acne is a common skin disorder of the pilosebaceous unit. In addition to genetic, hormonal and environmental factors, abnormal colonization by Propionibacterium acnes has been implicated in the occurrence of acne via the induction of inflammatory mediators. To gain more insight into the role that sebocytes play in the innate immune response of the skin, particularly in acne, we compared the antimicrobial peptide and proinflammatory cytokine/chemokine expression at mRNA and protein levels, as well as the viability and differentiation of SZ95 sebocytes in response to co-culture with representative isolates of P. acnes type IA and type IB as well as Escherichia coli-derived lipopolysaccharide (LPS). We found that, in vitro, P. acnes type IA and IB isolates and LPS induced human beta-defensin-2 and proinflammatory cytokine/chemokine expression, and influenced sebocyte viability and differentiation. Our results provide evidence that sebocytes are capable of producing proinflammatory cytokines/chemokines and antimicrobial peptides, which may have a role in acne pathogenesis. Furthermore, since P. acnes types IA and IB differentially affect both the differentiation and viability of sebocytes, our data demonstrate that different strains of P. acnes vary in their capacity to stimulate an inflammatory response within the pilosebaceous follicle.
Topics: Antimicrobial Cationic Peptides; Cell Line; Cell Survival; Coculture Techniques; Cytokines; DNA, Bacterial; Gene Expression; Humans; Lipopolysaccharides; Molecular Sequence Data; Phylogeny; Propionibacterium acnes; RNA; Rec A Recombinases; Sebaceous Glands; Sequence Analysis, DNA
PubMed: 16797202
DOI: 10.1016/j.micinf.2006.04.001