Tacrolimus suppresses atopic dermatitis-associated cytokines and chemokines in monocytes

Chang, Kai-Ting; Lin, Hugo You-Hsien; Kuo, Chang-Hung; Hung, Chih‐Hsing

doi:10.1016/j.jmii.2014.07.006

Cited by 37 publications

(20 citation statements)

References 43 publications

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“…D). We also investigated the production of several inflammatory mediators known to be present in AD lesions [IL‐1β , chemokine motif ligand 1 (CXCL1) , CXCL9 , and EPX ] and observed that they were all significantly reduced following IVM or BMV treatment (Fig. D).…”

Section: Resultsmentioning

confidence: 99%

Topical ivermectin improves allergic skin inflammation

Ventre

Rozières

Lenief

et al. 2017

Allergy

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Section: Resultsmentioning

confidence: 99%

Topical ivermectin improves allergic skin inflammation

Ventre

Rozières

Lenief

et al. 2017

Allergy

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“…These data are in contradiction with the findings reported by Chang et al . who described an inhibitory effect of tacrolimus on p-ERK but not on p38MAPK phosphorylation [ 26 ]. However, in contrast to the present study in which primary monocytes were investigated, the experiments by Chang et al .…”

Section: Discussionmentioning

confidence: 99%

“…The limited number of studies on the effect of tacrolimus on monocyte functions have been mostly performed in animal models, immortalized cell lines and cord blood cells. These studies report that tacrolimus can suppress the production of IL-1β, IL-10 and TNF-α by polyclonally activated monocytes [ 26 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Tacrolimus and Mycophenolic Acid on CD14+ Monocyte Activation and Function

et al. 2017

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Monocytes and macrophages play key roles in many disease states, including cellular and humoral rejection after solid organ transplantation (SOT). To suppress alloimmunity after SOT, immunosuppressive drug therapy is necessary. However, little is known about the effects of the immunosuppressive drugs tacrolimus and mycophenolic acid (MPA) on monocyte activation and function. Here, the effect of these immunosuppressants on monocytes was investigated by measuring phosphorylation of three intracellular signaling proteins which all have a major role in monocyte function: p38MAPK, ERK and Akt. In addition, biological functions downstream of these signaling pathways were studied, including cytokine production, phagocytosis and differentiation into macrophages. To this end, blood samples from healthy volunteers were spiked with diverse concentrations of tacrolimus and MPA. Tacrolimus (200 ng/ml) inhibited phosphorylation of p38MAPK by 30% (mean) in CD14+ monocytes which was significantly less than in activated CD3+ T cells (max 60%; p < 0.05). This immunosuppressive agent also partly inhibited p-AKT (14%). MPA, at a therapeutic concentration showed the strongest effect on p-AKT (27% inhibition). p-ERK was inhibited with a maximum of 15% after spiking with either tacrolimus or MPA. The production of IL-1β and phagocytosis by monocytes were not affected by tacrolimus concentrations, whereas MPA did inhibit IL-1β production by 50%. Monocyte/macrophage polarization was shifted to an M2-like phenotype in the presence of tacrolimus, while MPA increased the expression of M2 surface markers, including CD163 and CD200R, on M1 macrophages. These results show that tacrolimus and MPA do not strongly affect monocyte function, apart from a change in macrophage polarization, to a clinically relevant degree.

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“…The effects of these drugs on alloreactive T-cell function have been extensively characterized, but the knowledge of their effect on monocytes is limited [5]. The few in vitro studies that have been conducted in this respect have indicated that TAC and MPA affect cytokine production by monocytes [28,29]. Furthermore, TAC did not affect phagocytosis or production of IL-1β in vitro, whereas MPA did reduce the production of IL-1β [30].…”

Section: A C C E P T E Dmentioning

confidence: 99%

Pharmacodynamic Monitoring of Tacrolimus-Based Immunosuppression in CD14+ Monocytes After Kidney Transplantation

Kannegieter¹,

Hesselink²,

Dieterich³

et al. 2017

Therapeutic Drug Monitoring

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Tacrolimus suppresses atopic dermatitis-associated cytokines and chemokines in monocytes

Abstract: Tacrolimus suppressed LPS-induced MDC, I-309, IP-10, GRO-α, and TNF-α expressions in monocytes through the MAPK-ERK pathway; thus, tacrolimus may yield therapeutic efficacy by modulating AD-associated cytokines and chemokines.

Cited by 37 publications

References 43 publications

Topical ivermectin improves allergic skin inflammation

Topical ivermectin improves allergic skin inflammation

The Effect of Tacrolimus and Mycophenolic Acid on CD14+ Monocyte Activation and Function

Pharmacodynamic Monitoring of Tacrolimus-Based Immunosuppression in CD14+ Monocytes After Kidney Transplantation

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