Abstract
Chemokines are a burgeoning family of chemotactic cytokines displaying a broad array of functions such as regulation of homeostatic leukocyte traffic and development, as well as activating the innate immune system. Their role in controlling early and late inflammatory stages is now well recognized. An improper balance either in chemokine synthesis or chemokine receptor expression contributes to various pathological disorders making chemokines and their receptors a useful therapeutic target. Research in this area is progressing rapidly, and development of novel agents based on chemokine/chemokine receptors antagonist functions are emerging as attractive alternative drugs. Some of these novel agents include generation of chemokine-derived peptides (CDP) with potential agonist and antagonist effects on inflammation, cancer and against bacterial infections. CDP have been generated mainly from N- and C-terminus chemokine sequences with subsequent modifications such as truncations or elongations. In this review, we present a glimpse of the different pharmacological actions reported for CDP and our current understanding regarding the potential use of CDP alone or as part of the novel therapies proposed in the treatment of microbial infections and cancer.
Highlights
Chemokines are members of a superfamily of small proteins of pro-inflammatory mediators and potent leukocyte chemoattractants
VMIP-II, a chemokine encoded by human herpes virus 8 (HHV-8) [43] displays diverse interactions with both CC and CXC chemokine receptors and inhibits human immunodeficiency virus-1 (HIV-1) entry mediated through CCR3, CCR5, and CXCR4 [44]
It is well established that ELR+ CXC chemokines, such as CXCL1/GRO-α, CXCL2/GRO-β, CXCL3/GRO-γ, CXCL5/ENA-78, CXCL6/GSP-2, CXCL7/NAP-2, and CXCL8/IL-8, have shown to be potent angiogenic factors directly acting on CXCR1 and CXCR2 expressed on endothelial cells stimulating their proliferation, chemotaxis, and inhibiting apoptosis
Summary
Chemokines are members of a superfamily of small proteins of pro-inflammatory mediators and potent leukocyte chemoattractants They have been implicated in different activities, including regulation of inflammation, haemostasis, angiogenesis, and cell proliferation [1,2]. The ELR+ CXC chemokines, such as interleukin-8 (CXCL8/IL-8), are angiogenic, whereas most ELR− CXC chemokines, like Platelet Factor-4 (CXCL4/PF-4) inhibit angiogenesis [7,8,9]. This “ELR” motif appears to be important in the regulation of ligand/receptor interactions on neutrophils [10]. An increased knowledge of the mechanisms involved in chemokine-chemokine receptor activation may be useful in designing novel receptor antagonists
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