The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases

Abstract

Chemokines are small proteins that control several tissue functions, including cell recruitment and activation under homeostatic and inflammatory conditions. CXCL8 (interleukin-8) is a member of the chemokine family that acts on CXCR1 and CXCR2 receptors. CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, and CXCL7 are also ELR+ chemokine members that bind to these receptors, especially CXCR2. The majority of studies on the biology of CXCL8 and their receptors have been performed in polymorphonuclear leukocytes. However, many other cells express CXCR1/CXCR2, including epithelial, endothelial, fibroblasts and neurons, contributing to the biological effects of CXCL8. There is substantial amount of experimental data suggesting that CXCL8 and receptors contribute to elimination of pathogens, but may also contribute significantly to disease-associated processes, including tissue injury, fibrosis, angiogenesis and tumorigenesis. Here, we discuss the biology of CXCL8 family and the potential therapeutic use of antagonists or blockers of these molecules in the context of organ-specific diseases.

Keywords::

• acute and chronic inflammation
• chemoattractants
• clinical trials
• CXCL8
• CXCR1
• CXCR2
• infection

Acknowledgements

The authors are grateful to Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq, Fundação de Amparo à Pesquisa do Estado de Minas Gerais – FAPEMIG, European Community's Seventh Framework Programme (FP7-2007-2013) under grant agreement HEALTH-F4-2011-281608, by the financial support.

Financial & competing interests disclosure

MM Teixeira has received the financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq, Fundação de Amparo à Pesquisa do Estado de Minas Gerais – FAPEMIG and European Community's Seventh Framework Programme (FP7-2007-2013) under grant agreement HEALTH-F4-2011-281608. CC Garcia, FA Amaral and R Russo have received the financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq and Fundação de Amparo à Pesquisa do Estado de Minas Gerais – FAPEMIG. The authors have no conflicts of interest to declare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• CXCL8 was first cloned as a neutrophil-specific chemoattractant.

• In addition to CXCL8, the CXCL8 family comprises the chemokines CXCL1, CXCL2, CXCL3, CXCL5, CXCL6 and CXCL7, which share a common ELR (glutamic acid–leucine–arginine) motif and the CXCR1 and CXCR2 receptors.

• CXCR1 and CXCR2 are expressed on neutrophils at high levels but also on other leukocytes and other cell types. Hence, the benefits of blockade of CXCR1/2 may extend well beyond controlling neutrophil migration.

• There is much data demonstrating the expression and role for the CXCL8 family of chemokines in acute and chronic inflammatory conditions and cancer. These molecules may be, however, relevant for host immune responses against certain infections.

• Several inhibitors or antagonists for the CXCL8 family are available and currently being tested for the treatment of several acute and chronic inflammatory conditions of humans.

Notes