NDLI: Interplay between CXCR2 and BLT1 facilitates neutrophil infiltration and resultant keratinocyte activation in a murine model of imiquimod-induced psoriasis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ishii, Satoshi Yanagida, Keisuke Kita, Yoshihiro Sato, Shinichi Sumida, Hayakazu Shimizu, Takao Abe, Jun Matsushima, Kouji Nakamura, Motonao
Description	Author Affiliation: Sumida H ( Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan)
Abstract	Psoriasis is an inflammatory skin disease with accelerated epidermal cell turnover. Neutrophil accumulation in the skin is one of the histological characteristics of psoriasis. However, the precise mechanism and role of neutrophil infiltration remain largely unknown. In this article, we show that orchestrated action of CXCR2 and leukotriene B4 receptor BLT1 plays a key role in neutrophil recruitment during the development of imiquimod (IMQ)-induced psoriatic skin lesions in mice. Depletion of neutrophils with anti-Ly-6G Ab ameliorated the disease severity, along with reduced expression of proinflammatory cytokine IL-1ß in the skin. Furthermore, CXCR2 and BLT1 coordinately promote neutrophil infiltration into the skin during the early phase of IMQ-induced inflammation. In vitro, CXCR2 ligands augment leukotriene B4 production by murine neutrophils, which, in turn, amplifies chemokine-mediated neutrophil chemotaxis via BLT1 in autocrine and/or paracrine manners. In agreement with the increased IL-19 expression in IMQ-treated mouse skin, IL-1ß markedly upregulated expression of acanthosis-inducing cytokine IL-19 in human keratinocytes. We propose that coordination of chemokines, lipids, and cytokines with multiple positive feedback loops might drive the pathogenesis of psoriasis and, possibly, other inflammatory diseases as well. Interference to this positive feedback or its downstream effectors could be targets of novel anti-inflammatory treatment.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	9
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Keratinocytes Metabolism Neutrophil Infiltration Immunology Psoriasis Receptors, Interleukin-8b Receptors, Leukotriene B4 Adjuvants, Immunologic Toxicity Aminoquinolines Animals Chemotaxis, Leukocyte Disease Models, Animal Immunohistochemistry Mice Mice, Knockout Neutrophils Chemically Induced Real-time Polymerase Chain Reaction Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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