Selective inhibition and augmentation of alternative macrophage activation by progesterone.

Progesterone is the female sex hormone necessary for the maintenance of pregnancy, and is known to modulate macrophage activation. However, studies have concentrated exclusively on the ability of progesterone to negatively regulate the innate and classical pathways of activation, associated with nitric oxide (NO) and interleukin (IL)-12 production. Our aim was to examine the ability of progesterone to modulate alternative macrophage activation. Bone marrow cells were isolated and differentiated from male BALB/c mice, exposed to varying concentrations of progesterone and stimulated with lipopolysaccharide (LPS) (innate activation), IL-4 (alternative activation) or LPS in combination with IL-4. Our present study demonstrates that progesterone not only down-regulates inducible nitric oxide synthase 2 (iNOS) activity in macrophages but also arginase activity, in a dose-dependent manner, independent of the stimuli, whether it is induced by LPS (innate activation), IL-4 (alternative activation) or LPS in combination with IL-4. The ability of progesterone to down-modulate IL-4-induced cell surface expression of the mannose receptor further suggested a negative regulation of alternative macrophage activation by this hormone. Analysis of mRNA expression, by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), of genes associated with innate and alternative macrophage activation revealed that progesterone down-regulated LPS-induced macrophage nos2, argI and p40 (IL-12/IL-23) expression and IL-4-induced argI, mrc-1 and fizz1 expression. However, progesterone up-regulated IL-4-induced macrophage expression of ym1, while dectin-1 expression remained unaltered. Following treatment of macrophages with LPS and IL-4 in combination a similar pattern was observed, with the exception that progesterone up-regulated macrophage expression of fizz1 as well as ym1 and did not modify mrc-1 expression. Our data demonstrate for the first time that a hormone has the ability to regulate selectively the expression of different genes associated with alternative macrophage activation.

Menzies FM ，Henriquez FL ，Alexander J ，Roberts CW ... -  《-》

[Adipose-derived stem cells promote the polarization from M1 macrophages to M2 macrophages].

Yin X ，Pang C ，Bai L ，Zhang Y ，Geng L ... -  《-》

Sequential expression of macrophage anti-microbial/inflammatory and wound healing markers following innate, alternative and classical activation.

Menzies FM ，Henriquez FL ，Alexander J ，Roberts CW ... -  《-》

Markers of macrophage differentiation in experimental silicosis.

Misson P ，van den Brûle S ，Barbarin V ，Lison D ，Huaux F ... -  《JOURNAL OF LEUKOCYTE BIOLOGY》

The influence of ezetimibe on classical and alternative activation pathways of monocytes/macrophages isolated from patients with hypercholesterolemia.

Suchy D ，Łabuzek K ，Machnik G ，Okopień B ... -  《-》