Hoelscher, Christoph, Graeb, Jessica, Hoelscher, Alexandra, Mueller, Annie Linnea, Schaefer, Stephan C. and Rybniker, Jan (2020). Chemical p38 MAP kinase inhibition constrains tissue inflammation and improves antibiotic activity in Mycobacterium tuberculosis-infected mice. Sci Rep, 10 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Host-modulating therapies have become an important focus in the development of novel concepts for improved management of tuberculosis (TB). Previous in vitro studies revealed that the p38 MAP kinase signaling pathway coordinates several inflammatory and stress responses in Mycobacterium tuberculosis (Mtb)-infected host cells. Here we extend these findings and show that in vivo treatment of Mtb-infected C57BL/6 mice with doramapimod, a p38 MAP-kinase inhibitor, results in reduced inflammation, granuloma formation and lung pathology. Moreover, doramapimod, together with standard antibiotic treatment, significantly reduced lung and spleen mycobacterial loads compared to antibiotic treatment alone. Our in vivo data suggest the opportunity to repurpose p38 MAPK inhibitors for adjunct host directed therapies. We also provide first data on safety of p38 MAPK inhibition which is of relevance for future application of these substances in inflammatory diseases and concomitant TB.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hoelscher, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Graeb, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoelscher, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Annie LinneaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, Stephan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rybniker, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-323378
DOI: 10.1038/s41598-020-70184-x
Journal or Publication Title: Sci Rep
Volume: 10
Number: 1
Date: 2020
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BACTERIAL; THERAPYMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32337

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