Cellular zinc homeostasis modulates polarization of THP-1-derived macrophages

Dierichs, Laura; Kloubert, Veronika; Rink, Lothar

doi:10.1007/s00394-017-1491-2

Cited by 57 publications

(30 citation statements)

References 39 publications

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“…CD206, also known as mannose receptor 1 (MRC1), which our data suggest is not expressed by THP-1 under any conditions, has been reported to be expressed by THP-1 cells in response to IL-4 [22,38] or after differentiation to dendritic-like cells [39]. Other studies support a lack of expression of CD206 in both native [40] and polarized cells [41]. Compared to primary human macrophages, mRNA levels for MRC1 are very low [9].…”

Section: Thp-1 Macrophage Extracellular Marker Expression After Phenomentioning

confidence: 49%

Similarities and differences in surface receptor expression by THP-1 monocytes and differentiated macrophages polarized using seven different conditioning regimens

Forrester

Wassall

Hall

et al. 2018

Cellular Immunology

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Macrophages are key in orchestrating immune responses to micro-environmental stimuli, sensed by a complex set of surface receptors. The human cell line THP-1 has a monocytic phenotype, including the ability to differentiate into macrophages, providing a tractable, standardised surrogate for human monocyte-derived macrophages. Here we assessed the expression of 49 surface markers including Fc, complement, C-type lectin and scavenger receptors; TIMs; Siglecs; and co-stimulatory molecules by flow cytometry on both THP-1 monocytes and macrophages and following macrophage activation with seven standard conditioning/polarizing stimuli. Of the 34 surface markers detected on macrophages, 18 altered expression levels on activation. From these, expression of 9 surface markers were consistently altered by all conditioning regimens, while 9 were specific to individual polarizing stimuli. This study provides a resource for the study of macrophages and highlights that macrophage polarization states share much in common and the differences do not easily fit a simple classification system.

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Section: Thp-1 Macrophage Extracellular Marker Expression After Phenomentioning

confidence: 49%

Similarities and differences in surface receptor expression by THP-1 monocytes and differentiated macrophages polarized using seven different conditioning regimens

Forrester

Wassall

Hall

et al. 2018

Cellular Immunology

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“…Zinc deficiency reportedly increases inflammatory cytokine expression and suppresses T lymphocyte and cytokine production . The adherent (macrophages) and non‐adherent (lymphocytes) cells were separated from the spleen using a cell culture plate.…”

Section: Resultsmentioning

confidence: 99%

“…), suggesting that the increase in the expression of inflammatory cytokines is not due to the formation of additional M1 macrophages. Therefore, it is possible that zinc deficiency activates resident M1 macrophages in response to dermatitis or ROS . In contrast, zinc deficiency decreased the number of M2 macrophages (Fig.…”

Section: Discussionmentioning

confidence: 96%

Inflammatory response under zinc deficiency is exacerbated by dysfunction of the T helper type 2 lymphocyte–M2 macrophage pathway

et al. 2019

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Nutritional zinc deficiency leads to immune dysfunction and aggravates inflammation. However, the underlying mechanism remains unknown. In this study, the relationship between macrophage subtypes (M1 and M2) and helper T lymphocytes (Th1 and Th2) was investigated using the spleen from rats fed zinc-deficient or standard diet. In experiment I, 5week-old male Sprague-Dawley rats were fed a zinc-deficient diet (without zinc additives) or a standard diet (containing 0Á01% zinc) for 6 weeks. In experiment II, the rats were divided into four groups: one group was fed a standard diet for 6 weeks; two groups were fed zinc-deficient diets and were injected three times a week with either saline or interleukin-4 (IL-4) (zinc-deficient/IL-4 i.p.); a fourth group (zinc-deficient/standard) was fed a zinc-deficient diet for 6 weeks followed by a standard diet for 4 weeks. In experiment I; GATA-binding protein 3 (GATA-3) protein level, M2 macrophage, CD3 + CD8 + cells, and IL-4/IL-13-positive cells significantly decreased in the spleens of the zinc-deficient group. Additionally, IL-1b and macrophage inflammatory protein-1a (MIP-1a) mRNA levels significantly increased in the splenic macrophages of the zinc-deficient group. In experiment II; M2 macrophages, CD3 + CD8 + cells, IL-4/IL-13-positive cells, and GATA-3 protein levels significantly increased in the spleens of the zinc-deficient/IL-4 i.p. and zinc-deficient/standard groups. Furthermore, IL-1b and MIP-1a mRNA levels decreased in the splenic macrophages of the zinc-deficient/IL-4 i.p. and zinc-deficient/standard groups. Zinc deficiency-induced aggravated inflammation is related to Th2 lymphocytes and followed by the association with loss of GATA-3, IL-4 and anti-inflammatory M2 macrophages. Importantly, IL-4 injection or zinc supplementation can reverse the effects of zinc deficiency on immune function.

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“…Differences in effect are most probably due to divergent experimental conditions and cell types, such as duration and intensity of zinc supplementation or deficiency. Another group of signaling molecules whose phosphorylation status and activity is altered by zinc are STAT molecules, as was demonstrated for STAT1, STAT3, and STAT6 [ 145 , 146 ]. Investigations of the role of zinc signals in the regulation of STAT5 activity showed varying results and may depend on the signaling pathway [ 71 , 135 , 147 ].…”

Section: Effects Of Zinc In Immune Cell Signalingmentioning

confidence: 99%

Zinc as a Gatekeeper of Immune Function

2017

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After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.

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Cellular zinc homeostasis modulates polarization of THP-1-derived macrophages

Cited by 57 publications

References 39 publications

Similarities and differences in surface receptor expression by THP-1 monocytes and differentiated macrophages polarized using seven different conditioning regimens

Similarities and differences in surface receptor expression by THP-1 monocytes and differentiated macrophages polarized using seven different conditioning regimens

Inflammatory response under zinc deficiency is exacerbated by dysfunction of the T helper type 2 lymphocyte–M2 macrophage pathway

Zinc as a Gatekeeper of Immune Function

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