The axon guidance molecule Robo is a transmembrane protein which is conserved during evolution. Robo and its ligand, Slit, have been implicated in regulating many developmental processes, such as axon guidance, neuronal migration, tumor metastasis, angiogenesis, lung morphogenesis, kidney morphogenesis, heart morphogenesis, ovary development and gonad development. Robo function mainly depends on the binding of its Ig1 domain to the LRR-2 domain of Slit ligand. Meanwhile, Robo function is also mediated by binding to some signaling molecules, including the heparan sulfate proteoglycans (HSPGs), GTPase-activating proteins (GAPs) and tyrosine kinase Abelson. Several transcription factors, including Hox, Midline and Nkx2.9, were shown to regulate robo expression. In addition, alternative splicing and transport regulation also affect Robo function. In this review, we summarized the studies on the molecular structure, functions and molecular mechanism of Robo, which would propose a novel strategy for the research of neural development, as well as prevention and treatment of nervous system diseases and cancers.
Axons ; physiology ; Nerve Tissue Proteins ; physiology ; Receptors, Immunologic ; physiology

Acute-Phase Proteins ; physiology ; Carrier Proteins ; physiology ; Humans ; Membrane Glycoproteins ; physiology ; Receptors, Cell Surface ; physiology ; Receptors, Immunologic ; physiology ; Receptors, Scavenger ; Sepsis ; metabolism ; physiopathology ; Signal Transduction ; Toll-Like Receptors

Prostaglandin D2 (PGD2) is a major prostanoid, produced mainly by mast cells, in allergic diseases, including bronchial asthma. PGD2-induced vasodilatation and increased permeability are well-known classical effects that may be involved in allergic inflammation. Recently, novel functions of PGD2 have been identified. To date, D prostanoid receptor (DP) and chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) have been shown to be major PGD2-related receptors. These two receptors have pivotal roles mediating allergic diseases by regulating the functions of various cell types, such as TH2 cells, eosinophils, basophils, mast cells, dendritic cells, and epithelial cells. This review will focus on the current understanding of the roles of PGD2 and its metabolites in TH2 inflammation and the pathogenesis of bronchial asthma.
Asthma/*etiology/immunology ; Basophils/physiology ; Eosinophils/physiology ; Humans ; Mast Cells/physiology ; Prostaglandin D2/*physiology ; Receptors, Immunologic/physiology ; Receptors, Prostaglandin/physiology ; Th2 Cells/*immunology

This study was aimed to examine the expression and function of Slit/Robo family members in mouse ovary. Real-time PCR was used to assess the mRNA expression levels of Slit/Robo family members, and immunohistochemistry was used to examine the location of Slit2 and Robo1 in the ovary. The mRNA and protein expression levels of Slit2 and Robo1 in early-, middle- and late-phase corpus luteum (CL) were examined by real-time PCR and immunohistochemistry, respectively. Blocking agent ROBO1/Fc chimera was used in the luteal cells in vitro to examine the function of Slit/Robo signaling pathway in mouse CL. The results showed that, among the Slit/Robo family members, the expression levels of ligand Slit2 and receptor Robo1 were the highest in mouse ovarian tissue. Moreover, both of them were specifically expressed in mouse luteal cells. Compared with proestrus ovaries, the expression levels of Slit2 and Robo1 mRNA in the ovaries during diestrus were significantly up-regulated (P < 0.01, P < 0.001). The mRNA expression levels of Slit2 and Robo1 in late-phase CL were significantly increased when compared with pregnant CL. Furthermore, blocking Slit/Robo signaling pathway with ROBO1/Fc chimera in the luteal cells in vitro significantly decreased the apoptotic rate of late luteal cells. These results suggest that Slit/Robo family members are mainly expressed in the late-phase CL of ovary and participate in luteal cells apoptosis.
Animals ; Apoptosis ; Female ; Intercellular Signaling Peptides and Proteins ; physiology ; Luteal Cells ; cytology ; Mice ; Nerve Tissue Proteins ; physiology ; Pregnancy ; Receptors, Immunologic ; physiology

Alzheimer's disease (AD) is a most common neurodegenerative disease. The mechanisms underlying AD, especially late-onset AD, remain elusive. In the past few years, results from genome-wide association studies (GWAS) and systems approaches indicated that innate immune responses mediated by microglia played critical roles in AD. Functional analysis on animal models also showed that immune receptors or proteins expressed in microglia mediated Abeta-induced inflammation, or Abeta phagocytosis by microglia. Microglia plays double sword roles in AD. More work is warranted to elucidate the exact roles of microglia in AD, which will facilitate our better understanding of the mechanisms underlying AD.
Alzheimer Disease ; pathology ; Animals ; Disease Models, Animal ; Genome-Wide Association Study ; Humans ; Inflammation ; pathology ; Microglia ; physiology ; Phagocytosis ; Receptors, Immunologic ; physiology

Adaptor Proteins, Signal Transducing ; Animals ; Antigens, Differentiation ; physiology ; Asthma ; etiology ; Humans ; Immune Tolerance ; Immunity, Innate ; Membrane Glycoproteins ; physiology ; Myeloid Differentiation Factor 88 ; Proteins ; physiology ; Receptors, Cell Surface ; physiology ; Receptors, Immunologic ; physiology ; Signal Transduction ; Toll-Like Receptors

BACKGROUNDThe mechanisms of pathological retinal neovascularization (RNV) remain unknown. Several microRNAs were reported to be involved in the process of RNV. Oxygen-induced retinopathy (OIR) is a useful model to investigate RNV. Our present work explored the expression and the role of microRNA-128 (miR-218) in oxygen-induced RNV.

METHODSOIR was used to establish RNV model. The expression level of miR-218 in the retina from OIR mice was assessed by quantitative real-time reverse transcriptase polymerase chain reaction. Fluorescein angiography was performed in retinae of OIR mice, and RNV was quantified by hematoxylin and eosin staining to evaluate the effect of pCDH-CMV-miR-218 intravitreal injection on RNV in OIR mice. Roundabout 1 (Robo1) expression was detected by Western blotting in mouse retinal vascular endothelial cells expressing a high or low level of miR-218 and retinal tissues from OIR mice. Cell migration was evaluated by scratch wound assay.

RESULTSIn OIR mice, the expression level of miR-218 was significantly down-regulated (P = 0.006). Retinal Robo1 expression was significantly increased at both mRNA and protein levels (P = 0.001, 0.008; respectively). miR-218 intravitreal injection inhibited retinal angiogenesis in OIR mice, and the restoration of miR-218 in retina led to down-regulation of Robo1.

CONCLUSIONSOur experiments showed that restoration of miR-218 inhibited retinal angiogenesis via targeting Robo1. MiR-218 contributed to the inhibition of retinal angiogenesis and miR-218 might be a new therapeutic target for preventing RNV.

Animals ; Cell Movement ; Cells, Cultured ; Mice ; Mice, Inbred C57BL ; MicroRNAs ; physiology ; Nerve Tissue Proteins ; physiology ; Oxygen ; pharmacology ; Receptors, Immunologic ; physiology ; Retinal Neovascularization ; prevention & control

OBJECTIVETo study the effect of hyperoxia and paired immunoglobin-like receptor B (PirB) on rat oligodendrocyte precursor cells (OPCs) in vivo and the neuroprotective effects of 17β-estradiol (E2) on these cells.

METHODSRat OPCs were treated with different concentrations of E2 and the cells were harvested for RT‑qPCR analysis at different time points. PriB was silenced with small interfering siRNA. The effects of E2 treatment and silencing of PriB on OPCs viability and apoptosis under hyperoxic stimulation were detected using 3‑(4,5‑dimethylthi‑azol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis.

RESULTSHyperoxia induced apoptosis in OPCs and decreased their viability. E2 treatment markedly down-regulated the expression of PirB. E2 treatment or PirB silencing markedly decreased hyperoxia-induced apoptosis and increased cell viability in OPCs.

CONCLUSIONSE2 can protect OPCs from hyperoxia-induced apoptosis.

Animals ; Apoptosis ; drug effects ; Estradiol ; pharmacology ; Hyperoxia ; pathology ; Neuroprotective Agents ; pharmacology ; Oligodendroglia ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Immunologic ; physiology ; Stem Cells ; drug effects ; physiology

HLA-Cw belongs to classic HLA-I gene, HLA-Cw molecules have high polymorphism like HLA-A and B molecules. They distribute extensively on the surfaces of karyote, not only presenting endogenetic antigen to CD8+ T cells to induce specific killing effect, but also participating in immunologic reaction as the ligands of killer cell immunoglobulin-like receptor (KIR). Thus it has been valued for their relations to diseases and the functions in transplantation immunity, anti virus and anti-tumor immunity.
Autoimmune Diseases ; immunology ; Graft vs Host Disease ; etiology ; HLA-C Antigens ; genetics ; physiology ; Humans ; Neoplasms ; immunology ; Receptors, Immunologic ; metabolism ; Receptors, KIR ; Virus Diseases ; immunology

The profound graft-versus-leukemia (GVL) effect presented after allogeneic hematopoietic cell transplantation (allo-HSCT) has been evidenced. In contrast to T cell mediated GVL, natural killer (NK) cells recognize target cells and introduce GVL effect by using an integration of activating and inhibitory receptors. This review has summarized current literatures from 2001 - 2003 on human killer cell immunoglobulin receptors (KIR) and other NK cell receptors involved in recognition of tumor targets and the polymorphism of KIR genes of donor/recipient pairs of related and unrelated Allo-HSCT. KIR epitope mismatch may facilitate engraftment and reduce leukemia relapse post transplant by mediating lysis of recipient's cells and introducing GVL effect under the condition of KIR epitope mismatch. Clinical roles of KIR in Allo-HSCT and immunotherapy are discussed. Technologic approach in allogeneic reactive NK cells introduction, identification and selection in vitro, development of inhibitory receptor blockade as well as up-regulation of activating NK cells may significantly enhance GVL immune response. Further investigation on the regulation of KIR inhibitory receptors enables to design novel strategy in cancer immunotherapy over the forthcoming decade.
Graft vs Host Disease ; immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune Tolerance ; Killer Cells, Natural ; immunology ; Major Histocompatibility Complex ; Receptors, Immunologic ; chemistry ; genetics ; physiology ; Receptors, KIR ; Transplantation, Homologous