Macrophage M1/M2 polarization and rheumatoid arthritis: A systematic review

Tardito, Samuele; Martinelli, G.; Soldano, Stefano; Paolino, Sabrina; Pacini, G.; Patanè, Massimo; Alessandri, Elisa; Smith, Vanessa; Cutolo, Maurizio

doi:10.1016/j.autrev.2019.102397

Cited by 271 publications

(207 citation statements)

References 91 publications

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“…Although some positive effect was seen in diminishing the pain, MRI images showed no change in synovitis after anti-GM-CSF treatment (50). Wood et al (35) declared that sub-groups of synovial macrophages functions as a spectrum with different remodeling signatures and Tardito et al (51) emphasized the need of a not classical sub-division into M1 and M2 macrophages, but a M1 and M2 coexistence and equilibrium.…”

Section: Macrophages In Oamentioning

confidence: 99%

Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

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Cartilage lesions and osteoarthritis (OA) presents an ever-increasing clinical and socioeconomic burden. Synovial inflammation and articular inflammatory environment are the key factor for chondrocytes apoptosis and hypertrophy, ectopic bone formation and OA progression. To effectively treat OA, it is critical to develop a drug that skews inflammation toward a pro-chondrogenic microenvironment. In this narrative and critical review, we aim to see the potential use of immune cells modulation or cell therapy as therapeutic alternatives to OA patients. Macrophages are immune cells that are present in synovial lining, with different roles depending on their subtypes. These cells can polarize to pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, being the latter associated with wound-healing by the production of ARG-1 and pro-chondrogenic cytokines, such as IL-10, IL-1RA, and TGF-b. Emerging evidence reveals that macrophage shift can be determined by several stimuli, apart from the conventional in vitro IL-4, IL-13, and IL-10. Evidences show the potential of physical exercise to induce type 2 response, favoring M2 polarization. Moreover, macrophages in contact with oxLDL have effect on the production of anabolic mediators as TGF-b. In the same direction, type II collagen, that plays a critical role in development and maturation process of chondrocytes, can also induce M2 macrophages, increasing TGF-b. The mTOR pathway activation in macrophages was shown to be able to polarize macrophages in vitro, though further studies are required. The possibility to use mesenchymal stem cells (MSCs) in cartilage restoration have a more concrete literature, besides, MSCs also have the capability to induce M2 macrophages. In the other direction, M1 polarized macrophages inhibit the proliferation and viability of MSCs and impair their ability to immunosuppress the environment, preventing cartilage repair. Therefore, even though MSCs therapeutic researches advances, other sources of M2 polarization are attractive issues, and further studies will contribute to the possibility to manipulate this polarization and to use it as a therapeutic approach in OA patients.

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Section: Macrophages In Oamentioning

confidence: 99%

Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

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“…17 M1 macrophages are induced by interferon-γ or lipopolysaccharide, and secrete pro-inflammatory cytokines including interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α) and reactive oxygen species (ROS), to promote inflammation and impair implants. In contrast, M2 macrophages are induced by cytokines IL-4 and IL-10, 18,19 and secrete anti-inflammatory cytokines such as IL-10, along with various growth factors such as transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF), 1,25-dihydroxy vitamin D3 and bone morphogenetic protein (BMP) to suppress inflammation, promote extracellular matrix reconstruction and bone healing. [20][21][22] Recent studies have shown that the presence of chronic M1 macrophage at the bone-implant interface inhibited new bone formation and promoted implant inflammatory encapsulation.…”

Section: Introductionmentioning

confidence: 99%

<p>Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO<sub>2</sub> Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy</p>

Chen¹,

Guan²,

Ren³

et al. 2020

IJN

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Introduction: The bone regeneration of endosseous implanted biomaterials is often impaired by the host immune response, especially macrophage-related inflammation which plays an important role in the bone healing process. Thus, it is a promising strategy to design an osteo-immunomodulatory biomaterial to take advantage of the macrophage-related immune response and improve the osseointegration performance of the implant. Methods: In this study, we developed an antibacterial silver nanoparticle-loaded TiO 2 nanotubes (Ag@TiO 2-NTs) using an electrochemical anodization method to make the surface modification and investigated the influences of Ag@TiO 2-NTs on the macrophage polarization, osteo-immune microenvironment as well as its potential molecular mechanisms in vitro and in vivo. Results: The results showed that Ag@TiO 2-NTs with controlled releasing of ultra-low-dose Ag + ions had the excellent ability to induce the macrophage polarization towards the M2 phenotype and create a suitable osteo-immune microenvironment in vitro, via inhibiting PI3K/Akt, suppressing the downstream effector GLUT1, and activating autophagy. Moreover, Ag@TiO 2-NTs surface could improve bone formation, suppress inflammation, and promote osteo-immune microenvironment compared to the TiO 2-NTs and polished Ti surfaces in vivo. These findings suggested that Ag@TiO 2-NTs with controlled releasing of ultra-low-dose Ag + ions could not only inhibit the inflammation process but also promote the bone healing by inducing healing-associated M2 polarization. Discussion: Using this surface modification strategy to modulate the macrophage-related immune response, rather than prevent the host response, maybe a promising strategy for implant surgeries in the future.

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“…CCL2 is a member of the CC chemokine family that is chemotactic to monocytes and memory T lymphocytes [24,25] . After being recruited to local tissues, monocytes differentiate into macrophages subtypes that release various in ammatory factors or play a role in tissue remodeling [26,27] . A recent study found that the insu cient synthesis of an anti-in ammatory gene in monocyte-derived macrophages was associated with increased susceptibility to TAK [28] .…”

Section: Discussionmentioning

confidence: 99%

Therapeutic value of curcumin on the initiation and development of inflammation in Takayasu’s arteritis mediated by HSP65-induced CCL2 overexpression

Wang

Kong

et al. 2020

Preprint

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Background Takayasu’s arteritis (TAK) is a chronic inflammatory disease characterized by macrophage infiltration. During the active stage, aorta adventitial fibroblasts (AAFs) proliferate excessively and produce numerous pro-inflammatory factors in the adventitia, the primary target of TAK therapy. Although the monocyte chemokine, CCL2, may contribute to macrophage infiltration in TAK arteries, whether there is an associated relationship with HSP65 remains unknown. Moreover, there are no reports of the activation of AAFs to produce inflammatory factors involvement in TAK pathogenesis. TAK treatment is associated with several challenges and contradictions. Curcumin is a traditional Chinese medicine with anti-inflammatory effects; however, its effectiveness for TAK and the underlying mechanism remains unclear. Methods We first verified high HSP65 expression in the aortic adventitia of TAK patients by IHC. mRNA-seq was used to profile differentially expressed genes (DEGs) between AAFs stimulated by HSP65 with or without pretreatment with curcumin, and untreated AAFs. The key chemokine, CCL2, screened by mRNA-seq was detected in the adventitia of the TAK aorta, and its correlation with HSP65 expression was analyzed by double-labelled immunofluorescence. We subsequently explored how HSP65 affected the production of inflammatory factors by AAFs at a cellular level and the related signaling pathway. We explored whether curcumin could hinder this process and verified the effect of curcumin on the level of serum CCL2 in patients with TAK. Results HSP65 was highly expressed in the adventitia of TAK arteries. The DEG analysis showed a key role of CCL2. The expression of CCL2 in the adventitia of TAK arteries was significantly higher than that of healthy subjects, and was correlated with HSP65. HSP65 facilitated the production of CCL2, IL-6, and IL-1β by AAFs via activation of the TLR4-JAK2/AKT/STAT3 pathway, among which the change in CCL2 was the greatest. Curcumin treatment reversed HSP65-induced CCL2 upregulation in vitro, which was more obvious than that of MTX and tofacitinib. Finally, curcumin significantly downregulated the level of serum CCL2 in TAK patients. Conclusion HSP65 initiates and promotes TAK inflammation by upregulating CCL2 in AAFs through the JAK2/AKT/STAT3 pathway, whereas curcumin could reverse this process and slow the initiation and development of TAK.

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Macrophage M1/M2 polarization and rheumatoid arthritis: A systematic review

Cited by 271 publications

References 91 publications

Macrophage: A Potential Target on Cartilage Regeneration

Macrophage: A Potential Target on Cartilage Regeneration

<p>Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO<sub>2</sub> Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy</p>

Therapeutic value of curcumin on the initiation and development of inflammation in Takayasu’s arteritis mediated by HSP65-induced CCL2 overexpression

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