Treatment with TNF-α inhibitor rectifies M1 macrophage polarization from blood CD14+ monocytes in patients with psoriasis independent of STAT1 and IRF-1 activation

Lin, Shang-Hung; Chuang, Hung‐Yi; Ho, Ji-Chen; Lee, Chih‐Hung; Hsiao, Chang‐Chun

doi:10.1016/j.jdermsci.2018.05.009

Cited by 51 publications

(45 citation statements)

References 34 publications

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“…Monocytes were isolated directly from PBMCs using CD14 + MicroBeads (Miltenyi Biotec, Auburn, CA, USA) according to the manufacturer’s instructions. We have previously confirmed, using flow cytometry, that the purity of the CD14 + cells after selection was about 96.4% [27].…”

Section: Methodsmentioning

confidence: 91%

MiR-146a-5p Expression in Peripheral CD14+ Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast Activation, Bone Resorption, and Correlates with Clinical Response

Lin

et al. 2019

JCM

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In psoriatic arthritis (PsA), progressive bone destruction is mediated by monocyte-derived osteoclasts. MicroRNAs (miRNAs) regulate many pathophysiological processes; however, their function in PsA patient monocytes has not been examined. This study aims to address whether specific miRNAs in CD14+ monocytes and monocyte-derived osteoclasts cause active osteoclastogenesis in PsA patients. Candidate miRNAs related to monocyte activation (miR-146a-5p, miR-146b-5p and miR-155-5p) were measured in circulatory CD14+ monocytes collected from 34 PsA patients, 17 psoriasis without arthritis (PsO) patients, and 34 normal controls (NCs). CD14+ monocytes were cultured with media containing TNF-α and RANKL to differentiate into osteoclasts. Osteoclast differentiation and bone resorption were measured by TRAP immunostaining and dentin slice resorption, respectively. The results showed that the miR-146a-5p expression was higher in PsA patient-derived CD14+ monocytes compared to PsO and NCs. Activation and bone resorption were selectively enhanced in osteoclasts from PsA patients, but both were abrogated by RNA interference against miR-146a-5p. More importantly, after clinical improvement using biologics, the increased miR-146a-5p expression in CD14+ monocytes from PsA patients was selectively abolished, and associated with blood CRP level. Our findings indicate that miR-146a-5p expression in CD14+ monocytes derived from PsA patients correlates with clinical efficacy, and induction of osteoclast activation and bone resorption.

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Section: Methodsmentioning

confidence: 91%

MiR-146a-5p Expression in Peripheral CD14+ Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast Activation, Bone Resorption, and Correlates with Clinical Response

Lin

et al. 2019

JCM

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“…The dynamic equilibrium of M1/M2 benefits to balance inflammatory T cells (Th1 and Th17 cells) and anti-inflammatory T cells (Th2 and Treg cells) in quantity, proportion, and function [ 39 – 41 ]. In certain vascular inflammatory diseases, e.g., psoriasis, BD, and atherosclerosis, however, this balance is broken [ 42 – 44 ]. Under the stimulation from chronic inflammatory signals, macrophages are provoked mainly as M1, whereas M2 activation is relatively inhibited [ 42 , 45 ].…”

Section: Possible Mechanisms Of Macrophage Polarization In Vasculamentioning

confidence: 99%

“…Emerging evidence supports that the recruitment and activation of macrophages in psoriatic skin lesions/blood vessels is a key pathogenic factor in the uncontrolled cutaneous/vascular inflammation [ 7 , 104 , 105 ]. A study from Lin et al (2018) proved that a greatly high ratio of M1/M2 macrophages emerged from patients with severe psoriasis, and M1 in peripheral blood is absolutely superior to M2 [ 44 ]. Meanwhile, M1-related inflammatory cytokines obviously increase in psoriatic lesions, especially TNF- α .…”

Section: Macrophage Polarization In Vascular Dermatosismentioning

confidence: 99%

“…Although inflammatory cytokine antagonists have been gradually promoted in some autoimmune diseases recently, the application of exogenous anti-inflammatory factors is still limited to cell or animal models. For example, adalimumab as a TNF- α inhibitor could decrease the ratio of M1 to M2 macrophage in patients with psoriasis [ 44 ], while the cytokine IL-35 contributed to inhibiting the production of IL-6 and CXCL8 and alleviating the severe symptoms of IMQ-induced psoriasis-like mice via reducing the ratio of M1/M2 macrophages as well as the infiltration of M1 in local organs [ 142 ]. In the same way, Wu et al (2017) suggested that local administration of TNF- α and IL-1 β , produced from M1, would be a potential excellent option to IH through inducing endothelial-to-mesenchymal transition and accelerating hemangioma regression [ 89 ].…”

Section: Treatment Hotlinementioning

confidence: 99%

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Regulating the Polarization of Macrophages: A Promising Approach to Vascular Dermatosis

Peng

Xian

Liu

et al. 2020

Journal of Immunology Research

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Macrophages, a kind of innate immune cells, derive from monocytes in circulation and play a crucial role in the innate and adaptive immunity. Under the stimulation of the signals from local microenvironment, macrophages generally tend to differentiate into two main functional phenotypes depending on their high plasticity and heterogeneity, namely, classically activated macrophage (M1) and alternatively activated macrophage (M2). This phenomenon is often called macrophage polarization. In pathological conditions, chronic persistent inflammation could induce an aberrant response of macrophage and cause a shift in their phenotypes. Moreover, this shift would result in the alteration of macrophage polarization in some vascular dermatoses; e.g., an increase in proinflammatory M1 emerges from Behcet’s disease (BD), psoriasis, and systemic lupus erythematosus (SLE), whereas an enhancement in anti-inflammatory M2 appears in infantile hemangioma (IH). Individual polarized phenotypes and their complicated cytokine networks may crucially mediate in the pathological processes of some vascular diseases (vascular dermatosis in particular) by activation of T cell subsets (such as Th1, Th2, Th17, and Treg cells), deterioration of oxidative stress damage, and induction of angiogenesis, but the specific mechanism remains ambiguous. Therefore, in this review, we discuss the possible role of macrophage polarization in the pathological processes of vascular skin diseases. In addition, it is proposed that regulation of macrophage polarization may become a potential strategy for controlling these disorders.

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“…Monocytes were isolated directly from PBMCs using CD14+ MicroBeads (Miltenyi Biotec, Auburn, CA, USA) according to the manufacturer’s instructions. The purity of the CD14+ cells after the selection is above 95% using flow cytometry showed according to our previous study [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

Upregulation of miR-941 in Circulating CD14+ Monocytes Enhances Osteoclast Activation via WNT16 Inhibition in Patients with Psoriatic Arthritis

Lin

et al. 2020

IJMS

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Psoriatic arthritis (PsA) is a destructive joint disease mediated by osteoclasts. MicroRNAs (miRNAs) regulate several important pathways in osteoclastogenesis. We profiled the expression of miRNAs in CD14+ monocytes from PsA patients and investigated how candidate microRNAs regulate the pathophysiology in osteoclastogenesis. The RNA from circulatory CD14+ monocytes was isolated from PsA patients, psoriasis patients without arthritis (PsO), and healthy controls (HCs). The miRNAs were initially profiled by next-generation sequencing (NGS). The candidate miRNAs revealed by NGS were validated by PCR in 40 PsA patients, 40 PsO patients, and 40 HCs. The osteoclast differentiation and its functional resorption activity were measured with or without RNA interference against the candidate miRNA. The microRNA-941 was selectively upregulated in CD14+ monocytes from PsA patients. Osteoclast development and resorption ability were increased in CD14+ monocytes from PsA patients. Inhibition of miR-941 abrogated the osteoclast development and function while increased the expression of WNT16. After successful treatment, the increased miR-941 expression in CD14+ monocytes from PsA patients was revoked. The expression of miR-941 in CD14+ monocytes is associated with PsA disease activity. MiR-941 enhances osteoclastogenesis in PsA via WNT16 repression. The miR-941 could be a potential biomarker and treatment target for PsA.

show abstract

Treatment with TNF-α inhibitor rectifies M1 macrophage polarization from blood CD14+ monocytes in patients with psoriasis independent of STAT1 and IRF-1 activation

Cited by 51 publications

References 34 publications

MiR-146a-5p Expression in Peripheral CD14+ Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast Activation, Bone Resorption, and Correlates with Clinical Response

MiR-146a-5p Expression in Peripheral CD14+ Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast Activation, Bone Resorption, and Correlates with Clinical Response

Regulating the Polarization of Macrophages: A Promising Approach to Vascular Dermatosis

Upregulation of miR-941 in Circulating CD14+ Monocytes Enhances Osteoclast Activation via WNT16 Inhibition in Patients with Psoriatic Arthritis

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