M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

Fukui, Shoichi; Iwamoto, Naoki; Takatani, Ayuko; Isobe, Takashi; Shimizu, Toshimasa; Umeda, Masataka; Nishino, Ayako; Horai, Yoshiro; Hirai, Yasuko; Koga, Tomohiro; Kawashiri, Shin‐ya; Tamai, Mami; Ichinose, Kunihiro; Nakamura, Hideki; Origuchi, Tomoki; Masuyama, Ritsuko; Kosai, Kosuke; Yanagihara, Katsunori; Kawakami, Atsushi

doi:10.3389/fimmu.2017.01958

Cited by 170 publications

(119 citation statements)

References 27 publications

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“…[12][13][14][15]37 Several studies have reported that subtypes and inflammatory status of peripheral monocytes greatly influence the progress of inflammatory diseases. [16][17][18]38 For example, Cifani et al reported that AAD patients displayed the significantly increased CD14 ++ CD16classical monocytes in the peripheral blood. 15 In the present study, the percentage of CD14 + CD163 + CX3CR1 + M2-like monocytes were decreased in the AAD patients as compared with HD, leading to an increase in the ratio of M1/M2-like monocytes.…”

Section: Discussionmentioning

confidence: 99%

“…M1-like monocytes express the CD68 + CCR2 + cell marker whereas M2-like monocytes express the CD163 + CX3CR1 + cell marker. [16][17][18] M1-and M2-like monocytes has been reported to be discrepantly presented in patients with diabetes, with the ratio of M1/M2-like monocytes being closely associated with disease severity. 16 However, the proBDNF expression pattern in M1-and M2like monocytes and in monocytes from AAD patients is not known yet.…”

Section: Introductionmentioning

confidence: 99%

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The regulatory role of ProBDNF in monocyte function: Implications in Stanford type‐A aortic dissection disease

et al. 2019

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Brain-derived neurotrophic factor precursor (proBDNF) has been reported to strengthen the dysfunction of monocytes/macrophages in animal studies. However, it is still unknown the roles of proBDNF in the dysfunction of monocytes in the inflammatory diseases in humans. In the present study, we showed that proBDNF and pan neurotrophic receptor p75 were significantly upregulated in monocytes from healthy donors (HD) after lipopolysaccharide treatment. Exogenous proBDNF treatment upregulated CD40 and proinflammatory cytokines expression in monocytes including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. In Stanford type-A acute aortic dissection (AAD) patients, proBDNF was upregulated in CD14 + CD163 + CX3CR1 + M2-but not CD14 + CD68 + CCR2 + M1-like monocytes. In addition, sera from AAD patients activated gene expression of proinflammatory cytokines in cultured PBMCs from HD, which was attenuated by proBDNF monoclonal antibody (Ab-proB) treatment. These findings suggested that upregulation of proBDNF in M2-like monocytes may contribute to the proinflammatory response in the AAD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The regulatory role of ProBDNF in monocyte function: Implications in Stanford type‐A aortic dissection disease

et al. 2019

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“…Macrophage-mediated inflammation and tissue damage are features of many chronic inflammatory diseases (63,64). To date, C5orf30 has been associated with two autoimmune diseases, RA and primary biliary cirrhosis, which have a shared pathogenesis, including the skew of macrophages to the inflammatory phenotype and disease progression associated with increased local recruitment and activation of macrophage and fibroblast cells (17,18,65,66). In this study, we show C5orf30 to be inversely correlated with disease activity, systemic inflammation, and local TNF levels in early RA patients.…”

Section: Discussionmentioning

confidence: 99%

“…We uncover new insights into C5orf30 physiology and discover differential regulation of C5orf30 in M1-and M2-like macrophages. An imbalance of macrophage M1-M2 polarization has been associated with RA and multiple inflammatory conditions (13)(14)(15)(16)(17). Identification of the proteins associated with the dynamic changes of macrophages is crucial for revealing the molecular basis of disease progression (18,19) and to fuel the innovation pipeline for novel therapeutic strategies targeting inflammatory resolution rather than suppression (20)(21)(22)(23).…”

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confidence: 99%

The Autoimmune Susceptibility GeneC5orf30Regulates Macrophage-Mediated Resolution of Inflammation

Dorris

Tazzyman

Moylett

et al. 2019

The Journal of Immunology

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Genetic variants in C5orf30 have been associated with development of the autoimmune conditions primary biliary cirrhosis and rheumatoid arthritis. In rheumatoid arthritis, C5orf30 expression is cell-specific, with highest expression found in macrophages and synovial fibroblasts. C5orf30 is highly expressed in inflamed joints and is a negative regulator of tissue damage in a mouse model of inflammatory arthritis. Transcriptomic analysis from ultrasound-guided synovial biopsy of inflamed joints in a well characterized clinical cohort of newly diagnosed, disease-modifying antirheumatic drugs-naive rheumatoid arthritis patients was used to determine the clinical association of C5orf30 expression with disease activity. A combined molecular and computational biology approach was used to elucidate C5orf30 function in macrophages both in vitro and in vivo. Synovial expression of C5orf30 is inversely correlated with both clinical measures of rheumatoid arthritis disease activity and with synovial TNF mRNA expression. C5orf30 plays a role in regulating macrophage phenotype and is differentially turned over in inflammatory and anti-inflammatory macrophages. Inhibition of C5orf30 reduces wound healing/repair-associated functions of macrophages, reduces signaling required for resolution of inflammation, and decreases secretion of anti-inflammatory mediators. In an animal model of wound healing (zebrafish), C5orf30 inhibition increases the recruitment of macrophages to the wound site. Finally, we demonstrate that C5orf30 skews macrophage immunometabolism, demonstrating a mechanism for C5orf30-mediated immune regulation.

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“…The degree of synovial macrophage infiltration correlates with the severity of RA (29). Monocytes can differentiate into classically activated pro-inflammatory M1 macrophages to aggravate the RA symptom and alternatively into anti-inflammatory M2 macrophages to improve the RA phenotype (30). Therefore, we determined whether HJ influences the infiltration of articular macrophages and the M1/M2 subsets in cIA mice.…”

Section: Hj Inhibits the Expression Of Pro-inflammatory Mediators In mentioning

confidence: 99%

Humulus japonicus extract ameliorates collagen‑induced arthritis in mice through regulation of overall articular inflammation

et al. 2019

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Humulus japonicus (HJ) is a widely used herbal medicine in Asia with anti-oxidative, anti-microbial, and anti-inflammatory effects. We investigated the potential therapeutic effects of HJ in rheumatoid arthritis (RA) using a mouse model of collagen-induced arthritis (cIA) and a lipopolysaccharide-stimulated murine macrophage cell line (RAW 264.7). The cIA mice were administered 300 mg/kg HJ orally starting 3 days prior to second immunization. The clinical and histopathological findings were assessed in the paw of CIA mice. The levels of autoantibodies and inflammatory markers were determined in the plasma and cell culture supernatant, respectively. The expression at mRNA and protein levels was analyzed by reverse transcription quantitative-PcR and western blot analysis, respectively. HJ significantly decreased the gross arthritic scores and paw swelling in cIA mice. Furthermore, synovial inflammation, cartilage destruction, and bone erosion were markedly reduced by HJ. It also decreased the expression of inflammatory enzymes in both the paw of mice and RAW 264.7 cells. Moreover, the expression of genes related to all macrophages and pro-inflammatory M1 macrophage were significantly decreased, whereas the expression of anti-inflammatory M2 macrophage marker was markedly increased in the paw of HJ-treated cIA mice. In addition, HJ suppressed the levels of plasma anti-type II collagen antibody following the decreased expression of T helper type 1 (Th1) and Th2 cell-associated surface markers and cytokines in the paw. HJ also significantly inhibited the expression of IL-6 both in vitro and in vivo, followed by reduced STAT3 phosphorylation and expression in the paw of cIA mice. Finally, the expression of osteoclast-related genes was decreased in the paw of HJ-treated cIA mice. These findings suggest that HJ can play a role in suppressing the development of CIA by overall regulation of articular inflammation. This study should provide new insights into the use of HJ as a therapeutically effective natural product against RA.

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M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

Cited by 170 publications

References 27 publications

The regulatory role of ProBDNF in monocyte function: Implications in Stanford type‐A aortic dissection disease

The regulatory role of ProBDNF in monocyte function: Implications in Stanford type‐A aortic dissection disease

The Autoimmune Susceptibility GeneC5orf30Regulates Macrophage-Mediated Resolution of Inflammation

Humulus japonicus extract ameliorates collagen‑induced arthritis in mice through regulation of overall articular inflammation

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