title: 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 Ca(2+) 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 (STIM1(fl/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.
authors.affiliation: *Signal Transduction Laboratory, Comparative Medicine Branch, Integrated Laboratory Systems, Incorporated, Cellular and Molecular Pathology Branch,National Toxicology Program, and Special Techniques Group, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Natacha
authors.initials: N
authors.lastname: Steinckwich
authors.affiliation: *Signal Transduction Laboratory, Comparative Medicine Branch, Integrated Laboratory Systems, Incorporated, Cellular and Molecular Pathology Branch,National Toxicology Program, and Special Techniques Group, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Page
authors.initials: P
authors.lastname: Myers
authors.affiliation: *Signal Transduction Laboratory, Comparative Medicine Branch, Integrated Laboratory Systems, Incorporated, Cellular and Molecular Pathology Branch,National Toxicology Program, and Special Techniques Group, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Kyathanahalli S
authors.initials: KS
authors.lastname: Janardhan
authors.affiliation: *Signal Transduction Laboratory, Comparative Medicine Branch, Integrated Laboratory Systems, Incorporated, Cellular and Molecular Pathology Branch,National Toxicology Program, and Special Techniques Group, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Norris D
authors.initials: ND
authors.lastname: Flagler
authors.affiliation: *Signal Transduction Laboratory, Comparative Medicine Branch, Integrated Laboratory Systems, Incorporated, Cellular and Molecular Pathology Branch,National Toxicology Program, and Special Techniques Group, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: King
authors.affiliation: *Signal Transduction Laboratory, Comparative Medicine Branch, Integrated Laboratory Systems, Incorporated, Cellular and Molecular Pathology Branch,National Toxicology Program, and Special Techniques Group, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Petranka
authors.affiliation: *Signal Transduction Laboratory, Comparative Medicine Branch, Integrated Laboratory Systems, Incorporated, Cellular and Molecular Pathology Branch,National Toxicology Program, and Special Techniques Group, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA putney@niehs.nih.gov.
authors.forename: James W
authors.initials: JW
authors.lastname: Putney
mesh_terms: D000634:Aminoquinolines / Q000633:toxicity; D000818:Animals; D015220:Calcium Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004195:Disease Models, Animal; D018922:HL-60 Cells; D006801:Humans; D000077271:Imiquimod; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D020556:Neutrophil Infiltration / Q000502:physiology; D009504:Neutrophils / Q000473:pathology* / Q000502:physiology*; D011565:Psoriasis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D012867:Skin / Q000473:pathology / Q000503:physiopathology; D000071737:Stromal Interaction Molecule 1
chemical_list: D000634:Aminoquinolines; D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C103530:STIM1 protein, human; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D000077271:Imiquimod
keywords: calcium signaling; chronic inflammatory disease; leukocyte migration
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