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Impact of p38 mitogen-activated protein kinase inhibition on immunostimulatory properties of human 6-sulfo LacNAc dendritic cells

Langosch, Saskia; Wehner, Rebekka; Malecka, Ania; Franks, Hester A.; Schäkel, Knut; Bachmann, Michael; Jackson, Andrew M.; Schmitz, Marc

Authors

Saskia Langosch

Rebekka Wehner

Ania Malecka

HESTER FRANKS hester.franks@nottingham.ac.uk
Clinical Associate Professor

Knut Schäkel

Michael Bachmann

Marc Schmitz



Abstract

p38 Mitogen-activated protein kinase (MAPK) plays a crucial role in the induction and regulation of innate and adaptive immunity. Furthermore, p38 MAPK can promote tumor invasion, metastasis, and angiogenesis. Based on these properties, p38 MAPK inhibitors emerged as interesting candidates for the treatment of immune-mediated disorders and cancer. However, the majority of p38 MAPK inhibitor-based clinical trials failed due to poor efficacy or toxicity. Further studies investigating the influence of p38 MAPK inhibitors on immunomodulatory capabilities of human immune cells may improve their therapeutic potential. Here, we explored the impact of the p38 MAPK inhibitor SB203580 on the pro-inflammatory properties of native human 6-sulfo LacNAc dendritic cells (slanDCs). SB203580 did not modulate maturation of slanDCs and their capacity to promote T-cell proliferation. However, SB203580 significantly reduced the production of pro-inflammatory cytokines by activated slanDCs. Moreover, inhibition of p38 MAPK impaired the ability of slanDCs to differentiate naïve CD4(+) T cells into T helper 1 cells and to stimulate interferon-γ secretion by natural killer cells. These results provide evidence that SB203580 significantly inhibits various important immunostimulatory properties of slanDCs. This may have implications for the design of p38 MAPK inhibitor-based treatment strategies for immune-mediated disorders and cancer.

Citation

Langosch, S., Wehner, R., Malecka, A., Franks, H. A., Schäkel, K., Bachmann, M., …Schmitz, M. (2016). Impact of p38 mitogen-activated protein kinase inhibition on immunostimulatory properties of human 6-sulfo LacNAc dendritic cells. Immunobiology, 221(2), 166-174. https://doi.org/10.1016/j.imbio.2015.09.012

Journal Article Type Article
Acceptance Date Sep 7, 2015
Online Publication Date Sep 10, 2015
Publication Date Feb 29, 2016
Deposit Date May 23, 2017
Publicly Available Date May 23, 2017
Journal Immunobiology
Print ISSN 0171-2985
Electronic ISSN 1878-3279
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 221
Issue 2
Pages 166-174
DOI https://doi.org/10.1016/j.imbio.2015.09.012
Keywords Dendritic cells; T cells; p38 Mitogen-activated protein kinase; Tumor immunology; Immune-mediated disorders
Public URL http://eprints.nottingham.ac.uk/id/eprint/33656
Publisher URL http://www.sciencedirect.com/science/article/pii/S0171298515300632
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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