Role of the store‐operated calcium entry protein, STIM1, in neutrophil chemotaxis and infiltration into a murine model of psoriasis‐inflamed skin

ABSTRACT Stromal interaction molecule 1 (STIM1) is a Ca2+ sensor protein that initiates store‐operated calcium entry (SOCE). STIM1 is known to be involved in the chemoattractant signaling pathway for FPR1 in cell lines, but its role in in vivo functioning of neutrophils is unclear. Plaque‐type psori...

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Published in:The FASEB journal 2015-07, Vol.29 (7), p.3003-3013
Main Authors: Steinckwich, Natacha, Myers, Page, Janardhan, Kyathanahalli S., Flagler, Norris D., King, Debra, Petranka, John G., Putney, James W.
Format: Article
Language:English
Subjects:
Aminoquinolines - toxicity
Animals
Calcium Channels - deficiency
Calcium Channels - genetics
Calcium Channels - physiology
calcium signaling
Chemotaxis, Leukocyte - physiology
chronic inflammatory disease
Disease Models, Animal
HL-60 Cells
Humans
In Vitro Techniques
leukocyte migration
Membrane Proteins - antagonists & inhibitors
Membrane Proteins - genetics
Membrane Proteins - physiology
Mice
Mice, Knockout
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - genetics
Neoplasm Proteins - physiology
Neutrophil Infiltration - physiology
Neutrophils - pathology
Neutrophils - physiology
Psoriasis - chemically induced
Psoriasis - pathology
Psoriasis - physiopathology
Research Communication
RNA, Small Interfering - genetics
Signal Transduction
Skin - pathology
Skin - physiopathology
Stromal Interaction Molecule 1
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Summary:ABSTRACT Stromal interaction molecule 1 (STIM1) is a Ca2+ sensor protein that initiates store‐operated calcium entry (SOCE). STIM1 is known to be involved in the chemoattractant signaling pathway for FPR1 in cell lines, but its role in in vivo functioning of neutrophils is unclear. Plaque‐type psoriasis is a chronic inflammatory skin disorder associated with chemoattractants driving neutrophils into the epidermis. We investigated the involvement of STIM1 in neutrophil chemotaxis in vitro, as well as during chronic psoriatic inflammation. To this end, we used conditional knockout (KO) mice lacking STIM1 in cells of myeloid lineage (STIM1fl/fl LysM‐cre). We demonstrate that STIM1 is required for chemotaxis because of multiple chemoattractants in mouse neutrophils in vitro. Using an imiquimod‐induced psoriasis‐like skin model, we show that KO mice had less neutrophil infiltration in the epidermis than controls, whereas neither chemoattractant production in the epidermis nor macrophage migration was decreased. KO mice displayed a more rapid reversal of the outward signs of psoriasis (plaques). Thus, KO of STIM1 impairs neutrophil contribution to psoriatic inflammation. Our data provide new insights to our understanding of how STIM1 orchestrates the cellular behavior underlying chemotaxis and illustrate the important role of SOCE in a disease‐related pathologic model.—Steinckwich, N., Myers, P., Janardhan, K. S., Flagler, N. D., King, D., Petranka, J. G., Putney, J. W. Role of the store‐operated calcium entry protein, STIM1, in neutrophil chemotaxis and infiltration into a murine model of psoriasis‐inflamed skin. FASEB J. 29, 3003‐3013 (2015). www.fasebj.org
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.14-265215