4.7 Article

Human monocytes respond to lipopolysaccharide (LPS) stimulation in a sex-dependent manner

Journal

JOURNAL OF CELLULAR PHYSIOLOGY
Volume 237, Issue 1, Pages 580-588

Publisher

WILEY
DOI: 10.1002/jcp.30503

Keywords

17-beta-estradiol; chemotaxis; estrogen receptors; human monocytes; LPS; sex differences

Funding

  1. Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro
  2. Universita degli Studi di Sassari

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Monocytes play a critical role in inflammation and immune response, and their activity is sex-dependent. The study found that LPS treatment led to qualitative and quantitative sex differences in monocytes, with differences in autophagy, TNF-alpha release, chemotaxis, and estrogen receptor expression between male and female cells. These results indicate that sex plays a significant role in regulating monocytes' functions in a cell- and parameter-specific manner.
Monocytes play a critical role in inflammation and immune response, their activity being sex-dependent. However, the basis of sex differences is not well understood. Therefore, we investigated the lipopolysaccharide (LPS) effects on tumor necrosis factor-alpha (TNF-alpha) release, autophagy, and chemotaxis in freshly isolated monocytes from healthy young men and women. In basal conditions, male and female monocytes had similar TNF-alpha release, chemotaxis, and estrogen receptors (ER-alpha) and ER-beta expression, while the LC3II/I ratio was significantly higher in males. LPS treatment induced qualitative and quantitative sex differences. It reduced autophagy and increased TNF-alpha release only in male monocytes, while, chemotaxis was significantly influenced only in female cells. Moreover, it reduced the expression of ER-alpha only in female cells, while ER-beta expression was reduced in both sexes, but more markedly in female cells. Finally, the interplay between LPS treatment and 17-beta-estradiol (E-2) was present only in female cells. Globally, these findings expand the concept that sex plays a role in regulating monocytes' functions, being sex differences cell- and parameter-specific.

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