MiR-146a negatively regulates TLR2-induced inflammatory responses in keratinocytes

99Citations
Citations of this article
88Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Keratinocytes represent the first line of defense against pathogens in the skin and have important roles in initiating and regulating inflammation during infection and autoimmunity. Here we investigated the role of miR-146a in the regulation of the innate immune response of keratinocytes. Toll-like receptor 2 (TLR2) stimulation of primary human keratinocytes resulted in an NF-κB- and mitogen-activated protein kinase-dependent upregulation of miR-146a expression, which was surprisingly long lasting, contrasting with the rapid and transient induction of inflammatory mediators. Overexpression of miR-146a significantly suppressed the production of IL-8, CCL20, and tumor necrosis factor-α, which functionally suppressed the chemotactic attraction of neutrophils by keratinocytes. Inhibition of endogenous miR-146a induced the production of inflammatory mediators even in nonstimulated keratinocytes, and potentiated the effect of TLR2 stimulation. Transcriptomic profiling revealed that miR-146a suppresses the expression of a large number of immune-related genes in keratinocytes. MiR-146a downregulated interleukin-1 receptor-associated kinase 1 and TNF receptor-associated factor 6, two key adapter molecules downstream of TLR signaling, and suppressed NF-κB promoter-binding activity as shown by promoter luciferase experiments. Together, these data identify miR-146a as a regulatory element in keratinocyte innate immunity, which prevents the production of inflammatory mediators under homeostatic conditions and serves as a potent negative feedback regulator after TLR2 stimulation. © 2014 The Society for Investigative Dermatology.

References Powered by Scopus

Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

35996Citations
N/AReaders
Get full text

MicroRNAs: Genomics, Biogenesis, Mechanism, and Function

32016Citations
N/AReaders
Get full text

Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources

28712Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Transition from inflammation to proliferation: a critical step during wound healing

1247Citations
N/AReaders
Get full text

The dynamics of the skin’s immune system

436Citations
N/AReaders
Get full text

The immune functions of keratinocytes in skin wound healing

269Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Meisgen, F., Xu Landén, N., Wang, A., Réthi, B., Bouez, C., Zuccolo, M., … Pivarcsi, A. (2014). MiR-146a negatively regulates TLR2-induced inflammatory responses in keratinocytes. Journal of Investigative Dermatology, 134(7), 1931–1940. https://doi.org/10.1038/jid.2014.89

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 36

67%

Researcher 16

30%

Professor / Associate Prof. 1

2%

Lecturer / Post doc 1

2%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 24

43%

Biochemistry, Genetics and Molecular Bi... 12

21%

Immunology and Microbiology 11

20%

Medicine and Dentistry 9

16%

Article Metrics

Tooltip
Social Media
Shares, Likes & Comments: 21

Save time finding and organizing research with Mendeley

Sign up for free