Impairment of systemic DHA synthesis affects macrophage plasticity and polarization

TY - JOUR

T1 - Impairment of systemic DHA synthesis affects macrophage plasticity and polarization

T2 - implications for DHA supplementation during inflammation

AU - Talamonti, Emanuela

AU - Pauter, Anna M

AU - Asadi, Abolfazl

AU - Fischer, Alexander W

AU - Chiurchiù, Valerio

AU - Jacobsson, Anders

PY - 2017/8

Y1 - 2017/8

N2 - Docosahexaenoic acid (DHA) is an omega-3 fatty acid obtained from the diet or synthesized from alpha-linolenic acid through the action of fatty acid elongases (ELOVL) and desaturases. DHA plays important roles in the central nervous system as well as in peripheral organs and is the precursor of several molecules that regulate resolution of inflammation. In the present study, we questioned whether impaired synthesis of DHA affected macrophage plasticity and polarization both in vitro and in vivo models. For this we investigated the activation status and inflammatory response of bone marrow-derived M1 and M2 macrophages obtained from mice deficient of Elovl2 (Elovl2-/-), a key enzyme for DHA synthesis in mammals. Although both wild type and Elovl2-/-mice were able to generate efficient M1 and M2 macrophages, M1 cells derived from Elovl2-/-mice showed an increased expression of key markers (iNOS, CD86 and MARCO) and cytokines (IL-6, IL-12 and IL-23). However, M2 macrophages exhibited upregulated M1-like markers like CD80, CD86 and IL-6, concomitantly with a downregulation of their signature marker CD206. These effects were counteracted in cells obtained from DHA-supplemented animals. Finally, white adipose tissue of Elovl2-/-mice presented an M1-like pro-inflammatory phenotype. Hence, impairment of systemic DHA synthesis delineates an alteration of M1/M2 macrophages both in vitro and in vivo, with M1 being hyperactive and more pro-inflammatory while M2 less protective, supporting the view that DHA has a key role in controlling the balance between pro- and anti-inflammatory processes.

AB - Docosahexaenoic acid (DHA) is an omega-3 fatty acid obtained from the diet or synthesized from alpha-linolenic acid through the action of fatty acid elongases (ELOVL) and desaturases. DHA plays important roles in the central nervous system as well as in peripheral organs and is the precursor of several molecules that regulate resolution of inflammation. In the present study, we questioned whether impaired synthesis of DHA affected macrophage plasticity and polarization both in vitro and in vivo models. For this we investigated the activation status and inflammatory response of bone marrow-derived M1 and M2 macrophages obtained from mice deficient of Elovl2 (Elovl2-/-), a key enzyme for DHA synthesis in mammals. Although both wild type and Elovl2-/-mice were able to generate efficient M1 and M2 macrophages, M1 cells derived from Elovl2-/-mice showed an increased expression of key markers (iNOS, CD86 and MARCO) and cytokines (IL-6, IL-12 and IL-23). However, M2 macrophages exhibited upregulated M1-like markers like CD80, CD86 and IL-6, concomitantly with a downregulation of their signature marker CD206. These effects were counteracted in cells obtained from DHA-supplemented animals. Finally, white adipose tissue of Elovl2-/-mice presented an M1-like pro-inflammatory phenotype. Hence, impairment of systemic DHA synthesis delineates an alteration of M1/M2 macrophages both in vitro and in vivo, with M1 being hyperactive and more pro-inflammatory while M2 less protective, supporting the view that DHA has a key role in controlling the balance between pro- and anti-inflammatory processes.

KW - Adipose Tissue, White

KW - Animals

KW - Cell Polarity

KW - Cells, Cultured

KW - Docosahexaenoic Acids

KW - Inflammation

KW - Interleukin-12

KW - Interleukin-23

KW - Interleukin-6

KW - Macrophages

KW - Mice, Inbred C57BL

KW - Nitric Oxide Synthase Type II

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1007/s00018-017-2498-9

DO - 10.1007/s00018-017-2498-9

M3 - SCORING: Journal article

C2 - 28299384

VL - 74

SP - 2815

EP - 2826

JO - CELL MOL LIFE SCI

JF - CELL MOL LIFE SCI

SN - 1420-682X

IS - 15

ER -