Sebum lipids influence macrophage polarization and activation

Summary

Background

As lipids are known to regulate macrophage functions it is reasonable to suppose that a sebocyte – macrophage axis mediated by sebum lipids may exist.

Objective

To investigate if sebocytes could contribute to the differentiation, polarization and function of macrophages with their secreted lipids.

Methods

Oil-red-O lipid staining and Raman spectroscopy were used to assess the dermal lipid content and penetration. Immunohistochemistry was used to analyse the macrophage subsets. Human peripheral blood monocytes were differentiated in the presence of either supernatant from human SZ95 sebocytes or major sebum lipid components and activated with Propionibacterium acnes. Macrophage surface markers and their capacity to uptake FITC-Propionibacterium acnes were detected by FACS measurements. Cytokine protein levels were evaluated by ELISA and Western blot analysis.

Results

Sebaceous gland rich skin had an increased dermal lipid content compared to sebaceous gland poor skin to which all the tested sebum component lipids could contribute by penetrating through the dermo-epidermal barrier. Of the lipids, oleic and linoleic acids promoted monocyte differentiation into alternatively activated macrophages. Moreover, linoleic acid also had an anti-inflammatory effect in Propionibacterium acnes activated macrophages, inhibiting the secretion of IL-1B, IL-6 and TNF-Α. Squalene, palmitic, stearic and oleic acids augmented the secretion of IL-1B even in the absence of Propionibacterium acnes, while oleic acid had a selective effect of inducing IL-1B, but down-regulating IL-6 and TNF-A secretion.

Conclusions

Our results suggest a role for sebaceous glands in modulating innate immune responses via their secreted lipids that are of possible pathologic and therapeutic relevance.

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