Estrogen contributes to sex differences in M2a macrophages during multi-walled carbon nanotube-induced respiratory inflammation.

Autor: Ray JL; Center for Environmental Health Sciences, University of Montana, Missoula, Montana, USA., Postma B; Center for Environmental Health Sciences, University of Montana, Missoula, Montana, USA., Kendall RL; Center for Environmental Health Sciences, University of Montana, Missoula, Montana, USA., Ngo MD; Mater Research Institute, Translational Research Institute, The University of Queensland, Brisbane, Australia., Foo CX; Mater Research Institute, Translational Research Institute, The University of Queensland, Brisbane, Australia., Saunders B; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, Ohio, USA., Ronacher K; Mater Research Institute, Translational Research Institute, The University of Queensland, Brisbane, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia., Gowdy KM; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, Ohio, USA., Holian A; Center for Environmental Health Sciences, University of Montana, Missoula, Montana, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Jan; Vol. 38 (1), pp. e23350.
DOI: 10.1096/fj.202301571RR
Abstrakt: Lung diseases characterized by type 2 inflammation are reported to occur with a female bias in prevalence/severity in both humans and mice. This includes previous work examining multi-walled carbon nanotube (MWCNT)-induced eosinophilic inflammation, in which a more exaggerated M2a phenotype was observed in female alveolar macrophages (AMs) compared to males. The mechanisms responsible for this sex difference in AM phenotype are still unclear, but estrogen receptor (ER) signaling is a likely contributor. Accordingly, male AMs downregulated ERα expression after MWCNT exposure while female AMs did not. Thus, ER antagonist Fulvestrant was administered prior to MWCNT instillation. In females, Fulvestrant significantly attenuated MWCNT-induced M2a gene expression and eosinophilia without affecting IL-33. In males, Fulvestrant did not affect eosinophil recruitment but reduced IL-33 and M2a genes compared to controls. Regulation of cholesterol efflux and oxysterol synthesis is a potential mechanism through which estrogen promotes the M2a phenotype. Levels of oxysterols 25-OHC and 7α,25-OHC were higher in the airways of MWCNT-exposed males compared to MWCNT-females, which corresponds with the lower IL-1β production and greater macrophage recruitment previously observed in males. Sex-based changes in cholesterol efflux transporters Abca1 and Abcg1 were also observed after MWCNT exposure with or without Fulvestrant. In vitro culture with estrogen decreased cellular cholesterol and increased the M2a response in female AMs, but did not affect cholesterol content in male AMs and reduced M2a polarization. These results reveal the modulation of (oxy)sterols as a potential mechanism through which estrogen signaling may regulate AM phenotype resulting in sex differences in downstream respiratory inflammation.
(© 2023 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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