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Galectin-3 is an amplifier of the interleukin-1β-mediated inflammatory response in corneal keratinocytes

Uchino, Yuichi ; Woodward, Ashley M. ; Mauris, Jérôme ; Peterson, Kristoffer LU ; Verma, Priya LU ; Nilsson, Ulf J. LU ; Rajaiya, Jaya and Argüeso, Pablo (2018) In Immunology 154(3). p.490-499
Abstract

Interleukin-1β (IL-1β) is a potent mediator of innate immunity commonly up-regulated in a broad spectrum of inflammatory diseases. When bound to its cell surface receptor, IL-1β initiates a signalling cascade that cooperatively induces the expression of canonical IL-1 target genes such as IL-8 and IL-6. Here, we present galectin-3 as a novel regulator of IL-1β responses in corneal keratinocytes. Using the SNAP-tag system and digitonin semi-permeabilization, we show that recombinant exogenous galectin-3 binds to the plasma membrane of keratinocytes and is internalized into cytoplasmic compartments. We find that exogenous galectin-3, but not a dominant negative inhibitor of galectin-3 polymerization lacking the N-terminal domain,... (More)

Interleukin-1β (IL-1β) is a potent mediator of innate immunity commonly up-regulated in a broad spectrum of inflammatory diseases. When bound to its cell surface receptor, IL-1β initiates a signalling cascade that cooperatively induces the expression of canonical IL-1 target genes such as IL-8 and IL-6. Here, we present galectin-3 as a novel regulator of IL-1β responses in corneal keratinocytes. Using the SNAP-tag system and digitonin semi-permeabilization, we show that recombinant exogenous galectin-3 binds to the plasma membrane of keratinocytes and is internalized into cytoplasmic compartments. We find that exogenous galectin-3, but not a dominant negative inhibitor of galectin-3 polymerization lacking the N-terminal domain, exacerbates the response to IL-1β by stimulating the secretion of inflammatory cytokines. The activity of galectin-3 could be reduced by a novel d-galactopyranoside derivative targeting the conserved galactoside-binding site of galectins and did not involve interaction with IL-1 receptor 1 or the induction of endogenous IL-1β. Consistent with these observations, we demonstrate that small interfering RNA-mediated suppression of endogenous galectin-3 expression is sufficient to impair the IL-1β-induced secretion of IL-8 and IL-6 in a p38 mitogen-activated protein kinase-independent manner. Collectively, our findings provide a novel role for galectin-3 as an amplifier of IL-1β responses during epithelial inflammation through an as yet unidentified mechanism.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Corneal keratinocyte, Galectin-3, Innate immunity, Interleukin-1β, P38 mitogen-activated protein kinase
in
Immunology
volume
154
issue
3
pages
490 - 499
publisher
Wiley-Blackwell
external identifiers
  • scopus:85042119639
  • pmid:29359328
ISSN
0019-2805
DOI
10.1111/imm.12899
language
English
LU publication?
yes
id
e4c79196-8fa9-4514-8861-f070a81ff53a
date added to LUP
2018-03-16 08:06:13
date last changed
2022-03-17 06:22:02
@article{e4c79196-8fa9-4514-8861-f070a81ff53a,
  abstract     = {{<p>Interleukin-1β (IL-1β) is a potent mediator of innate immunity commonly up-regulated in a broad spectrum of inflammatory diseases. When bound to its cell surface receptor, IL-1β initiates a signalling cascade that cooperatively induces the expression of canonical IL-1 target genes such as IL-8 and IL-6. Here, we present galectin-3 as a novel regulator of IL-1β responses in corneal keratinocytes. Using the SNAP-tag system and digitonin semi-permeabilization, we show that recombinant exogenous galectin-3 binds to the plasma membrane of keratinocytes and is internalized into cytoplasmic compartments. We find that exogenous galectin-3, but not a dominant negative inhibitor of galectin-3 polymerization lacking the N-terminal domain, exacerbates the response to IL-1β by stimulating the secretion of inflammatory cytokines. The activity of galectin-3 could be reduced by a novel d-galactopyranoside derivative targeting the conserved galactoside-binding site of galectins and did not involve interaction with IL-1 receptor 1 or the induction of endogenous IL-1β. Consistent with these observations, we demonstrate that small interfering RNA-mediated suppression of endogenous galectin-3 expression is sufficient to impair the IL-1β-induced secretion of IL-8 and IL-6 in a p38 mitogen-activated protein kinase-independent manner. Collectively, our findings provide a novel role for galectin-3 as an amplifier of IL-1β responses during epithelial inflammation through an as yet unidentified mechanism.</p>}},
  author       = {{Uchino, Yuichi and Woodward, Ashley M. and Mauris, Jérôme and Peterson, Kristoffer and Verma, Priya and Nilsson, Ulf J. and Rajaiya, Jaya and Argüeso, Pablo}},
  issn         = {{0019-2805}},
  keywords     = {{Corneal keratinocyte; Galectin-3; Innate immunity; Interleukin-1β; P38 mitogen-activated protein kinase}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{3}},
  pages        = {{490--499}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Immunology}},
  title        = {{Galectin-3 is an amplifier of the interleukin-1β-mediated inflammatory response in corneal keratinocytes}},
  url          = {{http://dx.doi.org/10.1111/imm.12899}},
  doi          = {{10.1111/imm.12899}},
  volume       = {{154}},
  year         = {{2018}},
}