Immunomodulatory tetracyclines ameliorate DNBS-colitis: Impact on microRNA expression and microbiota composition

Article


Garrido-Mesa, J., Algieri, F., Rodríguez-Nogales, A., Vezza, T., Utrilla, M.P., Garcia, F., Chueca, N., Rodríguez-Cabezas, M.E., Garrido Mesa, N. and Gálvez, J. 2018. Immunomodulatory tetracyclines ameliorate DNBS-colitis: Impact on microRNA expression and microbiota composition. Biochemical Pharmacology. 155, pp. 524-536. https://doi.org/10.1016/j.bcp.2018.07.044
AuthorsGarrido-Mesa, J., Algieri, F., Rodríguez-Nogales, A., Vezza, T., Utrilla, M.P., Garcia, F., Chueca, N., Rodríguez-Cabezas, M.E., Garrido Mesa, N. and Gálvez, J.
Abstract

Objective:

The use of immunomodulatory antibiotics to simultaneously target different factors involved in intestinal inflammatory conditions is an interesting but understudied pharmacological strategy. A great therapeutic potential has been obtained with minocycline and doxycycline in experimental colitis. Therefore, understanding the contribution of the different activities of immunomodulatory tetracyclines is crucial for the improvement and translation of their use into clinic.
Design:

A comparative pharmacological study including tetracyclines and other antibiotic or immunomodulatory drugs was performed in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice. The correlation between the therapeutic efficacy of each drug and changes in the gut microbiota composition, markers of barrier integrity, inflammatory mediators, microRNAs and TLRs was analysed to identify the main mechanisms of action.
Results:

Tetracyclines counteracted most of the markers found altered in DNBS-colitis, which differed from effects of corticosteroid treatment. Of note, administration of tetracyclines led to increased mucosal protection, associated with up-regulated expression of CCL2, miR-142 and miR-375. All drugs with antibiotic activity ameliorated the progression of inflammation and reduced neutrophil-related genes, such as miR-223, despite their effects were not associated with restored intestinal dysbiosis. However, reduced bacterial richness was correlated with increased expression of TLR2 and TLR9 in antibiotic-treated groups and TLR6 was also up-regulated by the immunomodulatory tetracyclines with higher efficacy (doxycycline, minocycline and tigecycline).
Conclusion:

The anti-inflammatory effect of tetracyclines involves specific modifications in TLR and microRNA expression leading to an improved microbial-derived signalling and mucosal protection. These results support the potential of immunomodulatory tetracyclines to prevent inflammation-associated tissue damage in acute intestinal inflammation.

JournalBiochemical Pharmacology
Journal citation155, pp. 524-536
ISSN0006-2952
Year2018
PublisherElsevier
Accepted author manuscript
License
Digital Object Identifier (DOI)https://doi.org/10.1016/j.bcp.2018.07.044
Web address (URL)https://doi.org/10.1016/j.bcp.2018.07.044
Publication dates
Online02 Aug 2018
Publication process dates
Deposited09 Aug 2018
Accepted30 Jul 2018
FunderJunta de Andalucía
Spanish Ministry of Economy and Competitiveness
Instituto de Salud Carlos III
Junta de Andalucía
Spanish Ministry of Economy and Competitiveness
Spanish Ministry of Economy and Competitiveness
Instituto de Salud Carlos III
Copyright information© 2018 Elsevier
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Garrido-Mesa J et al. BCP_13227.pdf
License: CC BY-NC-ND 4.0

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