Increased serum CXCR2 ligand levels in livedo vasculopathy with winter ulcerations: Possible contribution of neutrophil recruitment to lesional skin

Yang, Lingli; Murota, Hiroyuki; Shindo, Shoko; Yang, Fei; Serada, Satoshi; Fujimoto, Minoru; Naka, Tetsuji; Katayama, Ichiro

doi:10.1016/j.jdermsci.2016.01.004

Cited by 3 publications

(1 citation statement)

References 10 publications

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“…Although, ABX-IL-8 (Abgenix, Fremont, CA), a fully humanized antibody against CXCL8, failed to show efficacy in phase II clinical trials, ABCream (Anogen, Missassauga, ON, Canada), a formulation of CXCL8-blocking monoclonal antibody is reported to be effective in psoriatic treatment and has been approved in China 214, 216. CXCR2 mediated neutrophil recruitment also contributes to other skin lesions, such as livedoid vasculopathy 217 and atopic dermatitis 218.…”

Section: The Cxcl8-cxcr1/2 Axis In Inflammatory Diseasesmentioning

confidence: 99%

Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases

Ha¹,

Debnath²,

Neamati³

2017

Theranostics

563

464

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The chemokine receptors CXCR1/2 and their ligand CXCL8 are essential for the activation and trafficking of inflammatory mediators as well as tumor progression and metastasis. The CXCL8-CXCR1/2 signaling axis is involved in the pathogenesis of several diseases including chronic obstructive pulmonary diseases (COPD), asthma, cystic fibrosis and cancer. Interaction between CXCL8 secreted by select cancer cells and CXCR1/2 in the tumor microenvironment is critical for cancer progression and metastasis. The CXCL8-CXCR1/2 axis may play an important role in tumor progression and metastasis by regulating cancer stem cell (CSC) proliferation and self-renewal. During the past two decades, several small-molecule CXCR1/2 inhibitors, CXCL8 releasing inhibitors, and neutralizing antibodies against CXCL8 and CXCR1/2 have been reported. As single agents, such inhibitors are expected to be efficacious in various inflammatory diseases. Several preclinical studies suggest that combination of CXCR1/2 inhibitors along with other targeted therapies, chemotherapies, and immunotherapy may be effective in treating select cancers. Currently, several of these inhibitors are in advanced clinical trials for COPD, asthma, and metastatic breast cancer. In this review, we provide a comprehensive analysis of the role of the CXCL8-CXCR1/2 axis and select genes co-expressed in this pathway in disease progression. We also discuss the latest progress in developing small-molecule drugs targeting this pathway.

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