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Macrophage‐activating lipopeptide‐2 and corticotropin‐releasing hormone stimulate the inflammatory signalling in human sebocytes through activation of stearoyl‐CoA desaturase and fatty acid desaturase 2
Author(s) -
Zouboulis C.C.,
Angres S.
Publication year - 2021
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.17016
Subject(s) - downregulation and upregulation , fads2 , endocrinology , medicine , secretion , fatty acid , biology , biochemistry , docosahexaenoic acid , polyunsaturated fatty acid , gene
Background The macrophage‐activating lipopeptide‐2 (MALP‐2) activates cells carrying a functional Toll‐like receptor (TLR)‐2/6. Human sebocytes express functional TLR‐2, TLR‐4 and CD14. Upregulation of stearoyl‐CoA desaturase (SCD) and fatty acid desaturase‐2 (FADS2) expression induces pro‐inflammatory sebaceous activity. On the other hand, corticotropin‐releasing hormone (CRH) is likely to serve as an autocrine stress hormone in human sebocytes. In addition to its antiproliferative, lipogenetic and androgen‐activating functions, CRH exhibits a pro‐inflammatory action and its expression is upregulated in acne‐involved sebaceous glands. Objective Determination of the pro‐inflammatory function of MALP‐2 and CRH and clarification of the option that MALP‐2 and/or CRH activity on human sebocytes might be mediated through SCD and/or FADS2. Methods SZ95 sebocytes were treated with MALP‐2, CRH and the SCD inhibitor/ligand FPCA. SCD, FADS2, TLR‐2 mRNA and protein levels and IL‐6 and IL‐8 secretion were investigated. Intracellular CRH levels were assessed under treatment with CRH, MALP‐2, linoleic acid and arachidonic acid. Phorbol 12‐myristate 13‐acetate and dexamethasone served as positive and negative controls, respectively. Results MALP‐2 upregulated SCD, FADS2, TLR‐2 mRNA and protein levels and IL‐6 and IL‐8 secretion from SZ95 sebocytes. Co‐incubation of SZ95 sebocytes with MALP‐2/FPCA did not affect the MALP‐2‐induced SCD mRNA upregulation but reduced FADS2 mRNA levels and inhibited IL‐8 secretion. CRH induced an early, low‐level SCD and FADS2 upregulation and TLR‐2 and IL‐8 secretion. High intracellular CRH concentrations could be detected early after CRH treatment and persisted up to 24 h. MALP‐2 stimulated intracellular CRH levels. Conclusions MALP‐2 stimulates the inflammatory signalling in human sebocytes through SCD and FADS2 activation. Inhibition of FADS2 mRNA levels and IL‐8 secretion through MALP‐2/FCPA co‐incubation and diminution of fatty acid unsaturation might lead to a reduction of pro‐inflammatory sebaceous lipids. CRH upregulates inflammatory signalling via the SCD/FADS2 pathway, and MALP‐2 selectively enhances CRH levels in human sebocytes.