Macrophage development and polarization in chronic inflammation

Motwani, Madhur P.; Gilroy, Derek W.

doi:10.1016/j.smim.2015.07.002

Cited by 95 publications

(82 citation statements)

References 171 publications

(196 reference statements)

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“…Macrophages are innate immune cells that are crucial for initiation, maintenance, and resolution of inflammation depending on their phenotypes, namely, proinflammatory M1‐like and proresolving, anti‐inflammatory M2‐like subtypes (16). Human M1 and M2 macrophages exposed to pathogenic bacteria produce differential LMs that distinguish their inflammatory or proresolving phenotypes: M1‐like mainly generate 5‐LOX– and COX‐2–derived PGs and LTs, whereas M2‐like produce predominantly 15‐LOX–derived SPMs, including LX, Rv, PD, and MaR1 (12).…”

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confidence: 99%

Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome

et al. 2019

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Nonsteroidal anti‐inflammatory drugs interfere with the metabolism of arachidonic acid to proinflammatory prostaglandins and leukotrienes by targeting cyclooxygenases (COXs), 5‐lipoxygenase (LOX), or the 5‐LOX–activating protein (FLAP). These and related enzymes act in conjunction with marked crosstalk within a complex lipid mediator (LM) network where also specialized proresolving LMs (SPMs) are formed. Here, we present how prominent LM pathways can be differentially modulated in human proinflammatory M1 and proresolving M2 macrophage phenotypes that, upon exposure to Escherichia coli, produce either abundant prostaglandins and leukotrienes (M1) or SPMs (M2). Targeted liquid chromatography–tandem mass spectrometry–based metabololipidomics was applied to analyze and quantify the specific LM profiles. Besides expected on‐target actions, we found that: 1) COX or 15‐LOX‐1 inhibitors elevate inflammatory leukotriene levels, 2) FLAP and 5‐LOX inhibitors reduce leukotrienes in M1 but less so in M2 macrophages, 3) zileuton blocks resolution‐initiating SPM biosynthesis, whereas FLAP inhibition increases SPM levels, and 4) that the 15‐LOX‐1 inhibitor 3887 suppresses SPM formation in M2 macrophages. Conclusively, interference with discrete LM biosynthetic enzymes in different macrophage phenotypes considerably affects the LM metabolomes with potential consequences for inflammation‐resolution pharmacotherapy. Our data may allow better appraisal of the therapeutic potential of these drugs to intervene with inflammatory disorders.—Werner, M., Jordan, P. M., Romp, E., Czapka, A., Rao, Z., Kretzer, C., Koeberle, A., Garscha, U., Pace, S., Claesson, H.‐E., Serhan, C. N., Werz, O., Gerstmeier, J. Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome. FASEB J. 33, 6140–6153 (2019). http://www.fasebj.org

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Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome

et al. 2019

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“…Our previous research have demonstrated that HMGB1 protein levels were elevated in the EAM heart (Su et al, ), meanwhile, the role of ANG II in inflammatory diseases has sparked great interest, and ANG II levels were also significantly increased in EAM (Lu et al, ). Furthermore, macrophages play a crucial role in determinant of disease development and regression (Motwani and Gilroy, ; Su et al, ), based on these investigations, we want to further investigate the effect of ANG II in mediating HMGB1 secretion in macrophages.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II enhances the acetylation and release of HMGB1 in RAW264.7 macrophage

Zhou

Chen

et al. 2018

Cell Biology International

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The high-mobility group box-1 (HMGB1), as a highly conserved ubiquitous DNA-binding protein, has been widely studied in various diseases, including inflammation and tumor; however, fewer studies were focused on the mechanisms controlling HMGB1 release compared with the function of HMGB1. Previous studies have proven that ANG II can act as a pro-inflammatory cytokine, both of HMGB1 and ANG II were significantly upregulated in autoimmune diseases; however, the exact role of ANG II in regulating HMGB1 release have not been shown. The present study was to define the effects of ANG II on macrophages and the possible mechanisms in controlling HMGB1 release. Our results showed that ANG II can induce M1 macrophage polarization through upregulated the expression of HMGB1 and caused acetylation of HMGB1 and release via its dissociation from SIRT1, which in a positive feedback upregulates ANG II. Subsequently, HMGB1 inhibitors can reduce the ANG II-elicited polarize of macrophage. Meanwhile, we show that JAK/STAT pathways play an essential role in ANG II-induced HMGB1 nuclear translocation, JAK/STAT specific inhibitors can inhibit ANG II-induced HMGB1 expression. Taken together, our results provide a novel evidence that HMGB1 play a critical role in ANG II mediated macrophage polarization, and we suggest that ANG II mediated HMGB1 release via dissociation from SIRT1, induce hyperacetylation of HMGB1, thus for subsequent release, suggesting that the angiotensin II receptor antagonist is a potential drug target for inhibiting HMGB1 release in inflammation diseases.

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“…Given the specificity of the abiotic transformation and the lability of 3,w er easoned that this molecule might also represent an overlooked intermediate in mammalian PG biosynthesis.W e, therefore,s urveyed lipid mediators in human monocyte-derived macrophages with an M1 phenotype that is known for substantial PG production during inflammation. [25,26] Stimulation of M1 with ionophore A23187 was used to induce PG biosynthesis. [27] Lipid mediator extracts were screened for 3 using the UHPLC-MS protocol described above.I ndeed, 3 was detected (63 pg 2 10 6 cells), besides 2 (109 pg 2 10 6 cells À1 )and 1 (5370 pg 2 10 6 cells À1 ), in stimulated M1 macrophages ( Figure 5).…”

Section: Angewandte Chemiementioning

confidence: 99%

15‐Hydroperoxy‐PGE₂: Intermediate in Mammalian and Algal Prostaglandin Biosynthesis

et al. 2019

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Arachidonic-acid-derived prostaglandins (PGs), specifically PGE 2 ,p lay ac entral role in inflammation and numerous immunological reactions.T he enzymes of PGE 2 biosynthesis are important pharmacological targets for antiinflammatory drugs.B esides mammals,c ertain edible marine algae possess ac omprehensive repertoire of bioactive arachidonic-acid-derived oxylipins including PGs that may account for food poisoning.D escribed here is the analysis of PGE 2 biosynthesis in the red macroalga Gracilaria vermiculophylla that led to the identification of 15-hydroperoxy-PGE 2 ,anovel precursor of PGE 2 and 15-keto-PGE 2 .Interestingly,this novel precursor is also produced in human macrophages where it represents akey metabolite in an alternative biosynthetic PGE 2 pathway in addition to the well-established arachidonic acid-PGG 2 -PGH 2 -PGE 2 route.T his alternative pathway of mammalian PGE 2 biosynthesis mayo pen novel opportunities to intervene with inflammation-related diseases.

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Macrophage development and polarization in chronic inflammation

Cited by 95 publications

References 171 publications

Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome

Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome

Angiotensin II enhances the acetylation and release of HMGB1 in RAW264.7 macrophage

15‐Hydroperoxy‐PGE₂: Intermediate in Mammalian and Algal Prostaglandin Biosynthesis

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Macrophage development and polarization in chronic inflammation

Cited by 95 publications

References 171 publications

Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome

Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome

Angiotensin II enhances the acetylation and release of HMGB1 in RAW264.7 macrophage

15‐Hydroperoxy‐PGE2: Intermediate in Mammalian and Algal Prostaglandin Biosynthesis

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15‐Hydroperoxy‐PGE₂: Intermediate in Mammalian and Algal Prostaglandin Biosynthesis