Histamine Increases Th2 Cytokine-Induced CCL18 Expression in Human M2 Macrophages

The chemokine CCL18 is produced in cells of the myelomonocytic lineage and represents one of the most highly expressed chemokines in lesional skin and serum of atopic dermatitis patients. We investigated the role of histamine in CCL18 production in human monocyte-derived M2 macrophages differentiate...

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Autores principales:	Susanne Mommert, Judith Tabea Schaper, Katrin Schaper-Gerhardt, Ralf Gutzmer, Thomas Werfel
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	macrophages CCL18 atopic dermatitis histamine Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/6f50d9f5a39f4efaa3e6812b3bec0a31
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spelling	oai:doaj.org-article:6f50d9f5a39f4efaa3e6812b3bec0a312021-11-11T17:07:18ZHistamine Increases Th2 Cytokine-Induced CCL18 Expression in Human M2 Macrophages10.3390/ijms2221116481422-00671661-6596https://doaj.org/article/6f50d9f5a39f4efaa3e6812b3bec0a312021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11648https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The chemokine CCL18 is produced in cells of the myelomonocytic lineage and represents one of the most highly expressed chemokines in lesional skin and serum of atopic dermatitis patients. We investigated the role of histamine in CCL18 production in human monocyte-derived M2 macrophages differentiated in the presence of M-CSF and activated with IL-4, IL-13 or with IL-10. Since expression and regulation of histamine H1 receptor (H1R), H2R and H4R by IL-4 and IL-13 on human M2 macrophages were described, we analyzed expression of the histamine receptors in response to IL-10 stimulation by quantitative RT-PCR. IL-10 upregulated H2R and downregulated H4R mRNA expression by trend in M2 macrophages. IL-10, but in a more pronounced manner, IL-4 and IL-13, also upregulated CCL18. Histamine increased the cytokine-induced upregulation of CCL18 mRNA expression by stimulating the H2R. This effect was stronger in IL-10-stimulated M2 macrophages where the upregulation of CCL18 was confirmed at the protein level by ELISA using selective histamine receptor agonist and antagonists. The histamine-induced CCL18 upregulation in IL-10-activated M2 macrophages was almost similar in cells obtained from atopic dermatitis patients compared to cells from healthy control persons. In summary, our data stress a new function of histamine showing upregulation of the Th2 cells attracting chemokine CCL18 in human, activated M2 macrophages. This may have an impact on the course of atopic dermatitis and for the development of new therapeutic interventions.Susanne MommertJudith Tabea SchaperKatrin Schaper-GerhardtRalf GutzmerThomas WerfelMDPI AGarticlemacrophagesCCL18atopic dermatitishistamineBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11648, p 11648 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	macrophages CCL18 atopic dermatitis histamine Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	macrophages CCL18 atopic dermatitis histamine Biology (General) QH301-705.5 Chemistry QD1-999 Susanne Mommert Judith Tabea Schaper Katrin Schaper-Gerhardt Ralf Gutzmer Thomas Werfel Histamine Increases Th2 Cytokine-Induced CCL18 Expression in Human M2 Macrophages
description	The chemokine CCL18 is produced in cells of the myelomonocytic lineage and represents one of the most highly expressed chemokines in lesional skin and serum of atopic dermatitis patients. We investigated the role of histamine in CCL18 production in human monocyte-derived M2 macrophages differentiated in the presence of M-CSF and activated with IL-4, IL-13 or with IL-10. Since expression and regulation of histamine H1 receptor (H1R), H2R and H4R by IL-4 and IL-13 on human M2 macrophages were described, we analyzed expression of the histamine receptors in response to IL-10 stimulation by quantitative RT-PCR. IL-10 upregulated H2R and downregulated H4R mRNA expression by trend in M2 macrophages. IL-10, but in a more pronounced manner, IL-4 and IL-13, also upregulated CCL18. Histamine increased the cytokine-induced upregulation of CCL18 mRNA expression by stimulating the H2R. This effect was stronger in IL-10-stimulated M2 macrophages where the upregulation of CCL18 was confirmed at the protein level by ELISA using selective histamine receptor agonist and antagonists. The histamine-induced CCL18 upregulation in IL-10-activated M2 macrophages was almost similar in cells obtained from atopic dermatitis patients compared to cells from healthy control persons. In summary, our data stress a new function of histamine showing upregulation of the Th2 cells attracting chemokine CCL18 in human, activated M2 macrophages. This may have an impact on the course of atopic dermatitis and for the development of new therapeutic interventions.
format	article
author	Susanne Mommert Judith Tabea Schaper Katrin Schaper-Gerhardt Ralf Gutzmer Thomas Werfel
author_facet	Susanne Mommert Judith Tabea Schaper Katrin Schaper-Gerhardt Ralf Gutzmer Thomas Werfel
author_sort	Susanne Mommert
title	Histamine Increases Th2 Cytokine-Induced CCL18 Expression in Human M2 Macrophages
title_short	Histamine Increases Th2 Cytokine-Induced CCL18 Expression in Human M2 Macrophages
title_full	Histamine Increases Th2 Cytokine-Induced CCL18 Expression in Human M2 Macrophages
title_fullStr	Histamine Increases Th2 Cytokine-Induced CCL18 Expression in Human M2 Macrophages
title_full_unstemmed	Histamine Increases Th2 Cytokine-Induced CCL18 Expression in Human M2 Macrophages
title_sort	histamine increases th2 cytokine-induced ccl18 expression in human m2 macrophages
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6f50d9f5a39f4efaa3e6812b3bec0a31
work_keys_str_mv	AT susannemommert histamineincreasesth2cytokineinducedccl18expressioninhumanm2macrophages AT judithtabeaschaper histamineincreasesth2cytokineinducedccl18expressioninhumanm2macrophages AT katrinschapergerhardt histamineincreasesth2cytokineinducedccl18expressioninhumanm2macrophages AT ralfgutzmer histamineincreasesth2cytokineinducedccl18expressioninhumanm2macrophages AT thomaswerfel histamineincreasesth2cytokineinducedccl18expressioninhumanm2macrophages
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Histamine Increases Th2 Cytokine-Induced CCL18 Expression in Human M2 Macrophages

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