Mantovani A, Bonecchi R, Locati MTuning inflammation and immunity by chemokine sequestration: decoys and more. Nat Rev Immunol 6:907-918

Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano, Milan, Italy and Istituto di Patologia Generale, Università degli Studi di Milano, Via Luigi Mangiagalli 31, 20133 Milan.
Nature reviews. Immunology (Impact Factor: 34.99). 01/2007; 6(12):907-18. DOI: 10.1038/nri1964
Source: PubMed


A set of chemokine receptors are structurally unable to elicit migration or conventional signalling responses after ligand engagement. These 'silent' (non-signalling) chemokine receptors regulate inflammatory and immune reactions in different ways, including by acting as decoys and scavengers. Chemokine decoy receptors recognize distinct and complementary sets of ligands and are strategically expressed in different cellular contexts. Importantly, viruses and parasites have evolved multiple strategies to elude chemokines, including the expression of decoy receptors. So, decoy receptors for chemokines represent a general strategy to tune, shape and temper innate and adaptive immunity.

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    • "The most clinically relevant human data on CXCL8 refer to the correlation between high serum levels of the chemokine and poor prognoses, [42] [43] suggesting that patients expressing high levels of inflammatory cytokines or affected by inflammatory types of cancers are at a high risk of having aggressive cancers. Cancers associated with inflammation generally display the characteristics of aggressiveness [15] [44]. Since CXCL8 is not the only chemokine expressed under such circumstances, determination of its specific role is difficult. "
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    ABSTRACT: Although the functions of chemokines in the regulation of immune processes have been studied in some detail, the role of these biomolecules in cancer is not fully understood. Chemokines mediate migration of immune cells and other functions related to immunity. They are also involved in oncogenesis and in tumor progression, invasion, and metastasis through mechanisms similar to their roles in immune functions. Various chemokines also promote cell proliferation and resistance to apoptosis of stressed cells. Consequently, chemokines and their receptors present potential therapeutic targets for anticancer drugs. The chemokine CXCL8, also known as interleukin-8 (IL8), is a proinflammatory molecule that has functions within the tumor microenvironment. Due to its potent angiogenic effects and the activity of the chemokine and its receptors in the promotion of invasion and metastasis, CXCL8 and its receptors are now considered as attractive targets for cancer therapy. This review relates the current understanding of the regulation, signaling, and functions of CXCL8 that contribute to tumor growth and metastasis, and of its role in drug response.
    Full-text · Article · Oct 2013
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    • "The healing properties of this family have been expanded to include an efficient repair and regeneration of mice liver with partial hepatectomy.29 There is growing evidence that this hepatic repair process is regulated by CXC chemokine receptor 2 (CXCR2),30,31 which commonly binds to members of the CXCL chemokine family,32,33 suggesting that the four chemokines may play a major role in repairing injured liver cells but further studies are needed. "
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    ABSTRACT: Despite the progress in our understanding of genes essential for stem cell regulation and development, little is known about the factors secreted by stem cells and their effect on tissue regeneration. In particular, the factors secreted by human CD34+ cells remain to be elucidated. We have approached this challenge by performing a cytokine/growth factor microarray analysis of secreted soluble factors in medium conditioned by adherent human CD34+ cells. Thirty-two abundantly secreted factors have been identified, all of which are associated with cell proliferation, survival, tissue repair, and wound healing. The cultured CD34+ cells expressed known stem cell genes such as Nanog, Oct4, Sox2, c-Kit and HoxB4. The conditioned medium containing the secreted factors prevented cell death in liver cells exposed to liver toxin in vitro via inhibition of the caspase-3 signalling pathway. More importantly, in vivo studies using animal models of liver damage demonstrated that injection of the conditioned medium could repair damaged liver tissue (significant reduction in the necroinflammatory activity), as well as enable the animals to survive. Thus, we demonstrate that medium conditioned by human CD34+ cells has the potential for therapeutic repair of damaged tissue in vivo.Molecular Therapy (2013); doi:10.1038/mt.2013.194.
    Full-text · Article · Aug 2013 · Molecular Therapy
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    • "CXC and CC chemokine genes are also found in several miniclusters or as a single-gene in the genome. Chemokines can be also classified based on their mode of expression and function [1, 7, 8]. Inflammatory chemokines such as CXCL8 (also known as IL-8) are upregulated under conditions of inflammation, while homeostatic chemokines such as CXCL12 (also known as SDF-1) are produced constitutively at noninflamed sites, controlling from cell trafficking in the embryo to leukocyte homing for immune surveillance. "
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    ABSTRACT: Chemokines are a large family of small cytokines that are involved in host defence and body homeostasis through recruitment of cells expressing their receptors. Their genes are known to undergo rapid evolution. Therefore, the number and content of chemokine genes can be quite diverse among the different species, making the orthologous relationships often ambiguous even between closely related species. Given that rodents and rabbit are useful experimental models in medicine and drug development, we have deduced the chemokine genes from the genome sequences of several rodent species and rabbit and compared them with those of human and mouse to determine the orthologous relationships. The interspecies differences should be taken into consideration when experimental results from animal models are extrapolated into humans. The chemokine gene lists and their orthologous relationships presented here will be useful for studies using these animal models. Our analysis also enables us to reconstruct possible gene duplication processes that generated the different sets of chemokine genes in these species.
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