Galectin-3 is an amplifier of the interleukin-1β-mediated inflammatory response in corneal keratinocytes
(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
- Uchino, Yuichi ; Woodward, Ashley M. ; Mauris, Jérôme ; Peterson, Kristoffer LU ; Verma, Priya LU ; Nilsson, Ulf J. LU ; Rajaiya, Jaya and Argüeso, Pablo
- organization
- publishing date
- 2018-02-15
- 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
-
- pmid:29359328
- scopus:85042119639
- 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
- 2024-04-01 00:59:12
@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}},
}