ABSTRACT
CXCL17, a novel member of the CXC chemokine class, has been implicated in several human pathologies, but its role in mediating immune response is not well understood. Characteristic features of immune response include resident macrophages orchestrating successive and structured recruitment of neutrophils and monocytes to the insult site. Here, we show that Cxcl17 knockout (KO) mice, compared with the littermate wild-type control mice, were significantly impaired in peritoneal neutrophil recruitment post-lipopolysaccharide (LPS) challenge. Further, the KO mice show dysregulated Cxcl1, Cxcr2, and interleukin-6 levels, all of which directly impact neutrophil recruitment. Importantly, the KO mice showed no difference in monocyte recruitment post-LPS challenge or in peritoneal macrophage levels in both unchallenged and LPS-challenged mice. We conclude that Cxcl17 is a proinflammatory chemokine and that it plays an important role in the early proinflammatory response by promoting neutrophil recruitment to the insult site.
Subject(s)
Chemokines, CXC , Lipopolysaccharides , Mice, Knockout , Neutrophils , Receptors, Interleukin-8B , Animals , Mice , Neutrophils/immunology , Neutrophils/metabolism , Receptors, Interleukin-8B/metabolism , Receptors, Interleukin-8B/genetics , Chemokines, CXC/metabolism , Chemokines, CXC/genetics , Lipopolysaccharides/pharmacology , Chemokine CXCL1/metabolism , Chemokine CXCL1/genetics , Interleukin-6/metabolism , Interleukin-6/genetics , Neutrophil Infiltration , Mice, Inbred C57BL , Inflammation/immunology , Inflammation/pathology , Inflammation/metabolism , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Monocytes/immunology , Monocytes/metabolismABSTRACT
Receptor for Advanced Glycation End product (RAGE) plays a crucial role in a variety of physiological and pathological processes due to its ability to bind a broad repertory of ligands. There are also multiple forms of RAGE that exist; some work on promoting feed-forward pathways while others perform inhibitory actions. This review focuses on the RAGE isoforms expression, its intracellular pathways activation via RAGE- ligand interaction, and its importance in the physiological and pathological process of the brain. Many studies have suggested that RAGE induces the pathophysiological changes in Alzheimer's disease (AD) by being an intermediator of inflammation and inducer of oxidative stress. The critical roles played by RAGE in AD include its involvement in amyloid-beta (Aß) production, clearance, synaptic impairment, and neuronal circuit dysfunction. RAGE-Aß interaction also mediates the bi-directional crosstalk between peripheral and central systems. This interaction underlies a potential molecular pathway that disrupts the material structure and physiology of the brain. This review highlights the structure-function relation for RAGEAß interaction and the role of RAGE as a potential target in the development of treatments for AD.
