Sebocytes contribute to skin inflammation by promoting the differentiation of T helper 17 cells

Mattii, M; Lovászi, Marianna; Garzorz, Natalie; Atenhan, A.; Quaranta, Maria; Lauffer, Felix; Konstantinow, Alexander; Küpper, M.; Zouboulis, Christos C.; Kemény, Lajos; Eyerich, Kilian; Schmidt‐Weber, Carsten B.; Törőcsik, Dániel; Eyerich, Stefanie

doi:10.1111/bjd.15879

Cited by 55 publications

(49 citation statements)

References 41 publications

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“…In conclusion, our previous and present data suggest that not only the microbiota and chemical content of human skin show three main topographical areas (dry, moist, oily/ sebaceous), but probably in correlation to this, the immune and barrier characteristics of these topographical regions are also distinct, which can make these skin regions become prone to the development of "region-specific" inflammatory skin diseases, like HS on AGR and acne (Mattii et al, 2018) and rosacea (Dajnoki et al, 2017) on sebaceous glandrich areas.…”

supporting

confidence: 49%

Apocrine Gland–Rich Skin Has a Non-Inflammatory IL-17–Related Immune Milieu, that Turns to Inflammatory IL-17–Mediated Disease in Hidradenitis Suppurativa

Jenei

Dajnoki

Medgyesi

et al. 2019

Journal of Investigative Dermatology

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supporting

confidence: 49%

Apocrine Gland–Rich Skin Has a Non-Inflammatory IL-17–Related Immune Milieu, that Turns to Inflammatory IL-17–Mediated Disease in Hidradenitis Suppurativa

Jenei

Dajnoki

Medgyesi

et al. 2019

Journal of Investigative Dermatology

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“…We found that noncytotoxic concentrations of VDM11 and AM404 (see Supplementary Figures S3, S4a, and S7) induced a moderate but significant increase in SLP (Figure 3a, and see Supplementary Figure S4b) and that VDM11 interfered with the proinflammatory effects of LPS (Figure 3b and c). Certain sebocyte-derived cytokines (e.g., IL-6) can induce differentiation of CD4 þ /CD45RA þ naïve T cells into T helper type 17 cells (Mattii et al, 2017), further supporting the concept that dysregulation of sebocyte biology can contribute not only to the development of acne, but also to other (partly) T helper type 17-driven inflammatory dermatoses, such as AD or psoriasis. Thus, the suppression of IL-6 expression and release that we have shown here (Figure 3b and c) is likely to be clinically relevant and promises to be beneficial in such conditions.…”

Section: Discussionmentioning

confidence: 59%

Endocannabinoid Tone Regulates Human Sebocyte Biology

Zákány

Oláh

Markovics

et al. 2018

Journal of Investigative Dermatology

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We have previously shown that endocannabinoids (eCBs) (e.g., anandamide) are involved in the maintenance of homeostatic sebaceous lipid production in human sebaceous glands and that eCB treatment dramatically increases sebaceous lipid production. Here, we aimed to investigate the expression of the major eCB synthesizing and degrading enzymes and to study the effects of eCB uptake inhibitors on human SZ95 sebocytes, thus exploring the role of the putative eCB membrane transporter, which has been hypothesized to facilitate the cellular uptake and subsequent degradation of eCBs. We found that the major eCB synthesizing (N-acyl phosphatidylethanolamine-specific phospholipase D, and diacylglycerol lipase-α and -β) and degrading (fatty acid amide hydrolase, monoacylglycerol lipase) enzymes are expressed in SZ95 sebocytes and also in sebaceous glands (except for diacylglycerol lipase-α, the staining of which was dubious in histological preparations). eCB uptake-inhibition with VDM11 induced a moderate increase in sebaceous lipid production and also elevated the levels of various eCBs and related acylethanolamides. Finally, we found that VDM11 was able to interfere with the proinflammatory action of the TLR4 activator lipopolysaccharide. Collectively, our data suggest that inhibition of eCB uptake exerts anti-inflammatory actions and elevates both sebaceous lipid production and eCB levels; thus, these inhibitors might be beneficial in cutaneous inflammatory conditions accompanied by dry skin.

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“…Keratinocytes elicit and maintain the skin immune response through the secretion of soluble factors, including cytokines, as well as antimicrobial peptides (Nagy et al, 2005). Sebocytes in follicles colonized with C. acnes have shown increased cyclooxygenase-II (COX-II) expression (Makrantonaki et al, 2011;Mattii et al, 2018). The production of excess PGE 2 results in sebaceous gland enlargement and increased sebum production, favoring C. acnes proliferation (Ottaviani et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Exploring the Anti-Acne Potential of Impepho [Helichrysum odoratissimum (L.) Sweet] to Combat Cutibacterium acnes Virulence

et al. 2020

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The Gram-positive bacterium Cutibacterium acnes (previously Propionibacterium acnes), plays an important role in the pathogenesis and progression of the dermatological skin disorder acne vulgaris. The methanolic extract of Helichrysum odoratissimum (L.) Sweet (HO-MeOH) was investigated for its ability to target bacterial growth and pathogenic virulence factors associated with acne progression. The gas chromatography-mass spectrometry (GC-MS) analysis of HO-MeOH identified a-humulene (3.94%), acurcumene (3.74%), and caryophyllene (8.12%) as major constituents, which correlated with previous reports of other Helichrysum species. The HO-MeOH extract exhibited potent antimicrobial activity against C. acnes (ATCC 6919) with a minimum inhibitory concentration (MIC) of 7.81 µg/ml. It enhanced the antimicrobial activity of benzoyl peroxide (BPO). The extract showed high specificity against C. acnes cell aggregation at sub-inhibitory concentrations, preventing biofilm formation. Mature C. acnes biofilms were disrupted at a sub-inhibitory concentration of 3.91 µg/ml. At 100 µg/ml, HO-MeOH reduced interleukin-1a (IL-1a) cytokine levels in C. acnes-induced human keratinocytes (HaCaT) by 11.08%, highlighting its potential as a comedolytic agent for the treatment of comedonal acne. The extract exhibited a 50% inhibitory concentration (IC 50 ) of 157.50 µg/ ml against lipase enzyme activity, an enzyme responsible for sebum degradation, ultimately causing inflammation. The extract's anti-inflammatory activity was tested against various targets associated with inflammatory activation by the bacterium. The extract inhibited pro-inflammatory cytokine levels of IL-8 by 48.31% when compared to C. acnes-induced HaCaT cells at 7.81 µg/ml. It exhibited cyclooxygenase-II (COX-II) enzyme inhibition with an IC 50 of 22.87 µg/ml. Intracellular nitric oxide (NO) was inhibited by 40.39% at 7.81 µg/ml when compared with NO production in lipopolysaccharide (LPS)induced RAW264.7 cells. The intracellular NO inhibition was potentially due to the 2.14 fold reduction of inducible nitric oxide synthase (iNOS) gene expression. The HO-MeOH extract exhibited an IC 50 of 145.45 µg/ml against virulent hyaluronidase enzyme activity, Frontiers in Pharmacology | www.frontiersin.org January 2020 | Volume 10 | Article 1559 1 which is responsible for hyaluronan degradation and scar formation. This study provides scientific validation for the traditional use of H. odoratissimum as an ointment for pimples, not only due to its ability to control C. acnes proliferation but also due to its inhibitory activity on various targets associated with bacterial virulence leading to acne progression.

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Sebocytes contribute to skin inflammation by promoting the differentiation of T helper 17 cells

Cited by 55 publications

References 41 publications

Apocrine Gland–Rich Skin Has a Non-Inflammatory IL-17–Related Immune Milieu, that Turns to Inflammatory IL-17–Mediated Disease in Hidradenitis Suppurativa

Apocrine Gland–Rich Skin Has a Non-Inflammatory IL-17–Related Immune Milieu, that Turns to Inflammatory IL-17–Mediated Disease in Hidradenitis Suppurativa

Endocannabinoid Tone Regulates Human Sebocyte Biology

Exploring the Anti-Acne Potential of Impepho [Helichrysum odoratissimum (L.) Sweet] to Combat Cutibacterium acnes Virulence

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