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Galectin‐3 is an amplifier of the interleukin‐1 β ‐mediated inflammatory response in corneal keratinocytes
Author(s) -
Uchino Yuichi,
Woodward Ashley M.,
Mauris Jérôme,
Peterson Kristoffer,
Verma Priya,
Nilsson Ulf J.,
Rajaiya Jaya,
Argüeso Pablo
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12899
Subject(s) - galectin , biology , microbiology and biotechnology , secretion , inflammation , small interfering rna , immunology , transfection , biochemistry , gene
Summary Interleukin‐1 β ( IL ‐1 β ) 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 ‐1 β 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 ‐1 β 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 ‐1 β 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 ‐1 β . Consistent with these observations, we demonstrate that small interfering RNA ‐mediated suppression of endogenous galectin‐3 expression is sufficient to impair the IL ‐1 β ‐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 ‐1 β responses during epithelial inflammation through an as yet unidentified mechanism.