Granulocyte–macrophage colony-stimulating factor primes interleukin-13 production by macrophages via protease-activated receptor-2

Aoki, Manabu; Yamaguchi, Rui; Yamamoto, Tomohisa; Ishimaru, Yasuji; Ono, Tomomichi; Sakamoto, Arisa; Narahara, Sayoko; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

doi:10.1016/j.bcmd.2015.01.007

Cited by 13 publications

(13 citation statements)

References 35 publications

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“…IL-13 can also derive from a type 2 lymphocyte immune response [28][29][30], and therefore we investigated T cell subsets present in this model. We assessed gene expression of TBET for Th1 cells [31] and GATA3 for Th2 and other type 2 cells [32][33][34][35].…”

Section: T Cell Responses Are Not Required For the Observed M2 Maturamentioning

confidence: 99%

Phosphocholine‐containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states

Trial

Cieslik

Entman

2016

Immunity, Inflammation and Disease

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IntroductionWe studied monocyte transendothelial migration and subsequent polarization into M1/M2 macrophages in response to C‐reactive protein (CRP) with two disease‐related ligands: (1) phosphocholine (PC) and (2) multilamellar liposomes containing both unoxidized and oxidized forms of the lipid, phosphatidylcholine. These ligands differ in biological origin: PC is present on bacterial cell walls while oxidized lipids are present in atherogenic lipids.MethodsWe used an in vitro model of human monocyte transendothelial migration and assessed the polarization of monocytes and T cells and signaling through Fcγ receptors in monocytes.ResultsCRP without ligands did not promote M2 macrophage differentiation over background levels. However, when paired with either ligand, it increased M2 numbers. M2 differentiation was dependent on IL‐13, and in the case of CRP with PC, was associated with a Th2 response. Paradoxically, while CRP with PC initiated a Th2 response, the combination of liposomes with CRP resulted in a Th1 response without any change in Th2 numbers despite association with M2 macrophage polarization. To resolve the conundrum of an anti‐inflammatory macrophage response coexisting with a proinflammatory T cell response, we investigated signaling of CRP and its ligands through Fcγ receptors, which leads to macrophage activation independent of T cell signaling. We found that CRP plus PC acted via FcγRI, whereas CRP with liposomes bound to FcγRII. Both were activating signals as evidenced by SYK phosphorylation.ConclusionWe conclude that CRP with ligands can promote M2 macrophage differentiation to fibroblasts through FcγR activation, and this may result in an anti‐inflammatory influence despite a proinflammatory T cell environment caused by oxidized lipids. The potential relationship of this mechanism to chronic inflammatory disease is discussed.

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Section: T Cell Responses Are Not Required For the Observed M2 Maturamentioning

confidence: 99%

Phosphocholine‐containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states

Trial

Cieslik

Entman

2016

Immunity, Inflammation and Disease

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“…HNE activates TLR4 through TRAF6 activation (Pham, 2006). It has also been reported that lipopolysaccharide induces IL-12p40 (Das et al, 2011), but HNE does not induce IL-12 mRNA expression (Aoki et al, 2015). Based on these reports, the present study was performed to investigate the influence of PAR-2 activation by a native peptide agonist (neutrophil elastase), a synthetic peptide agonist (2-furoyl-LIGRLOamide), or a nonpeptide (AC-264613) agonist on IRF5 expression and IL-12p40 production by GM-CSF-dependent macrophages.…”

Section: Introductionmentioning

confidence: 93%

A protease‐activated receptor 2 agonist (AC‐264613) suppresses interferon regulatory factor 5 and decreases interleukin‐12p40 production by lipopolysaccharide‐stimulated macrophages: Role of p53

Yamaguchi

Yamamoto

Sakamoto

et al. 2016

Cell Biology International

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The transcription factor interferon regulatory factor 5 (IRF5) has a key role in the production of interleukin (IL)-12 by macrophages. IRF5 is also a central mediator of toll-like receptor signaling and is a direct target of p53. Activation of protease-activated receptor 2 (PAR-2) upregulates p53 and suppresses apoptosis. This study investigated the influence of human neutrophil elastase (HNE) and PAR-2 agonists on expression of IRF5 and IL-12p40 by macrophages stimulated with lipopolysaccharide. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent macrophages showed upregulation of IRF5 expression, while HNE reduced expression of p53 and IRF5 in a concentration-dependent manner. HNE also caused a concentration-dependent decrease of IRF5 in macrophages transfected with small interfering RNA to silence p53, while silencing of β-arrestin 2 blunted the reduction of p53 or IRF5 by HNE. Incubation of macrophages with a PAR-2 agonist, AC-264613, caused a decrease of IRF5 expression and also significantly reduced p53 protein expression. HNE upregulated the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) and caused transactivation of TLR4, while AC-264613 did not promote TLR4 transactivation. In conclusion, the PAR-2 agonist AC-264613 attenuated IRF5-associated IL-12p40 production by macrophages.

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“…On days 3 and 6 of culture, the cells were washed and fresh medium containing GM-CSF was added. On day 9 cells were utilized as GM-CSF-dependent macrophages in this study [1].…”

Section: Induction Of Macrophages From Adherent Monocytes and Stimulamentioning

confidence: 99%

“…We recently reported that GM-CSF upregulates PAR-2 protein production by macrophages [1]. PARs are G protein-coupled receptors that are activated by proteolytic cleavage of the amino-terminus and these receptors act as sensors for extracellular proteases.…”

Section: Introductionmentioning

confidence: 99%

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Mechanism of interleukin-13 production by granulocyte-macrophage colony-stimulating factor-dependent macrophages via protease-activated receptor-2

Yamaguchi

Yamamoto

Sakamoto

et al. 2015

Blood Cells, Molecules, and Diseases

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Granulocyte–macrophage colony-stimulating factor primes interleukin-13 production by macrophages via protease-activated receptor-2

Cited by 13 publications

References 35 publications

Phosphocholine‐containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states

Phosphocholine‐containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states

A protease‐activated receptor 2 agonist (AC‐264613) suppresses interferon regulatory factor 5 and decreases interleukin‐12p40 production by lipopolysaccharide‐stimulated macrophages: Role of p53

Mechanism of interleukin-13 production by granulocyte-macrophage colony-stimulating factor-dependent macrophages via protease-activated receptor-2

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