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21.
The functional characterisation of CK-1, a putative CC chemokine from rainbow trout (Oncorhynchus mykiss) 总被引:1,自引:0,他引:1
Recently a number of cytokine homologs have been cloned in teleost fish, including several that resemble chemokines, but to date few have been confirmed using functional assays. Chemokines are a family of cytokines that are able to induce chemotaxis in leucocytes. In this study CK-1, a rainbow trout chemokine, was functionally characterised. Recombinant CK-1 is able to attract rainbow trout peripheral blood leucocytes (PBL) in a micro-chemotaxis chamber. A greater number of PBLs migrated in response to CK-1 than to negative controls, either media alone or equivalent concentrations of beta2M, while comparable numbers migrated to the positive control, recombinant human C5a. The tissue distribution of CK-1 mRNA was also assessed by Northern blotting of RT-PCR and showed that expression is constitutive in the liver and gut, and is inducible by intraperitoneal injection of phytohemagglutinin in PBL and the head-kidney. Continuous cell lines generated from the gut and pituitary gland of the rainbow trout also express CK-1 message, whilst Southern analysis shows that CK-1 is a single copy gene. Finally, CK-1 shows the greatest amino acid similarity CCL20/LARC/Mip-3alpha as well as similar gene structure and expression pattern. 相似文献
22.
Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines 总被引:8,自引:0,他引:8
Arenberg DA Keane MP DiGiovine B Kunkel SL Strom SR Burdick MD Iannettoni MD Strieter RM 《Cancer immunology, immunotherapy : CII》2000,49(2):63-70
Bronchogenic carcinoma is the leading cause of malignancy-related mortality in the United States, with an overall 5-year
survival rate of less than 15%. This aggressive behavior reflects, among other traits, the capacity of the tumor to evade
normal host immune defenses, and to induce a pro-angiogenic environment. A central feature of any immune response toward tumors
is the recruitment of specific immune cell populations. In the present study we investigated the infiltration of monocytes
in human specimens of non-small-cell lung cancer (NSCLC). The presence of macrophages in NSCLC tumors was documented by immunohistochemistry.
In vitro chemotaxis assays demonstrated higher monocyte chemotactic activity in NSCLC tumor homogenates than in normal lung
tissue. We next investigated the expression of CC chemokines within specimens of NSCLC tumors. Levels of the CC chemokines
were higher in NSCLC tumor tissue than in normal lung tissue. Immunolocalization showed that the cells associated with antigenic
CC chemokines were the malignant tumor cells, as well as occasional stromal cells. Maximal inhibition of monocyte chemotaxis
induced by NSCLC in vitro occurred in the presence of neutralizing antibodies to MCP-1 and MIP-1β. On follow-up of 15 patients
in whom we quantified macrophage infiltration, we found that those with recurrence of disease had higher levels of macrophage
infiltration in their initial tumors. However, the functional significance of CC-chemokine-mediated macrophage infiltration
into NSCLC remains to be determined.
Received: 12 November 1999 / Accepted: 10 December 1999 相似文献
23.
Plasma membrane is a multifunctional structure that acts as the initial barrier against infection by intracellular pathogens. The productive HIV-1 infection depends upon the initial interaction of virus and host plasma membrane. Immune cells such as CD4 + T cells and macrophages contain essential cell surface receptors and molecules such as CD4, CXCR4, CCR5 and lipid raft components that facilitate HIV-1 entry. From plasma membrane HIV-1 activates signaling pathways that prepare the grounds for viral replication. Through viral proteins HIV-1 hijacks host plasma membrane receptors such as Fas, TNFRs and DR4/DR5, which results in immune evasion and apoptosis both in infected and uninfected bystander cells. These events are hallmark in HIV-1 pathogenesis that leads towards AIDS. The interplay between HIV-1 and plasma membrane signaling has much to offer in terms of viral fitness and pathogenicity, and a better understanding of this interplay may lead to development of new therapeutic approaches. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking. 相似文献
24.
The present study showed a wide presence of CCL28 in mouse CNS, including cerebral, cerebellum, brain stem and spinal cord. In hippocampus, the expression of CCL28 at both mRNA and protein level was clarified. The CCL28 expression was mainly localized in pyramidal cells of CA area, granular cells of dentate gyrus and some interneurons in CA area and hilus. Double-labelling immunocytochemistry revealed that most of calbindin, calretinin and parvalbumin immunopositive neurons expressed CCL28. During and after pilocarpine induced status epilepticus (SE), a down-regulated expression of CCL28 in hippocampal interneurons in the CA1 area and in the hilus of the dentate gyrus was demonstrated. The present study may, therefore provide evidence that CCL28 may have a novel role in CNS and may be involved in the loss of hippocampal interneurons, and subsequent disinhibition of pyramidal neurons. 相似文献
25.
Molecular characterization and gene expression of a CXC chemokine gene from Japanese flounder Paralichthys olivaceus 总被引:1,自引:0,他引:1
Chemokines are small, secreted cytokine peptides that have the ability to recruit a wide range of immune cells to sites of infection and disease. A novel CXC chemokine was obtained from Japanese flounder Paralichthys olivaceus. This chemokine cDNA contains an open reading frame of 333 nucleotides encoding 111 amino acid residues containing four conserved cysteine residues. The gene is composed of four exons and three introns as are those of mammalian and fish CXC chemokines. Results of homology and phylogenetic analysis revealed that the Japanese flounder CXC chemokine is closest to CXCL13 subgroup. The gene was expressed in immune-related organs, including head kidney, trunk kidney, spleen and peripheral blood leukocytes (PBLs). Japanese flounder CXC chemokine gene expression was observed at 3 and 6h after induction by LPS, but not at 3 and 6h after induction by poly I:C. These results suggest that the Japanese flounder CXC chemokine is probably associated with inflammatory as well as homeostatic functions. 相似文献
26.
Monica A. Thomas Becky J. Buelow Amanda M. Nevins Stephanie E. Jones Francis C. Peterson Rebekah L. Gundry Mitchell H. Grayson Brian F. Volkman 《The Journal of biological chemistry》2015,290(7):4528-4536
CCL28 is a human chemokine constitutively expressed by epithelial cells in diverse mucosal tissues and is known to attract a variety of immune cell types including T-cell subsets and eosinophils. Elevated levels of CCL28 have been found in the airways of individuals with asthma, and previous studies have indicated that CCL28 plays a vital role in the acute development of post-viral asthma. Our study builds on this, demonstrating that CCL28 is also important in the chronic post-viral asthma phenotype. In the absence of a viral infection, we also demonstrate that CCL28 is both necessary and sufficient for induction of asthma pathology. Additionally, we present the first effort aimed at elucidating the structural features of CCL28. Chemokines are defined by a conserved tertiary structure composed of a three-stranded β-sheet and a C-terminal α-helix constrained by two disulfide bonds. In addition to the four disulfide bond-forming cysteine residues that define the traditional chemokine fold, CCL28 possesses two additional cysteine residues that form a third disulfide bond. If all disulfide bonds are disrupted, recombinant human CCL28 is no longer able to drive mouse CD4+ T-cell chemotaxis or in vivo airway hyper-reactivity, indicating that the conserved chemokine fold is necessary for its biologic activity. Due to the intimate relationship between CCL28 and asthma pathology, it is clear that CCL28 presents a novel target for the development of alternative asthma therapeutics. 相似文献
27.
Duan M Kazmierski WM Chong PY Deanda F Edelstein M Ferris R Peckham J Wheelan P Xiong Z Zhang H Nishizawa R Takaoka Y 《Bioorganic & medicinal chemistry letters》2011,21(21):6470-6475
A novel series of pyridyl carboxamide-based CCR5 inhibitors was designed, synthesized, and demonstrated to be highly potent against HIV-1 infection in both HOS and PBL assays. Attempts to evaluate this series of compounds in a rat PK model revealed its instability in rat plasma. A hypothesis for this liability was proposed, and strategies to overcome this issue were pursued, leading to discovery of highly potent 40 and 41, which featured dramatically improved rat PK profiles. 相似文献
28.
Zheng C Cao G Xia M Feng H Glenn J Anand R Zhang K Huang T Wang A Kong L Li M Galya L Hughes RO Devraj R Morton PA Rogier DJ Covington M Baribaud F Shin N Scherle P Diamond S Yeleswaram S Vaddi K Newton R Hollis G Friedman S Metcalf B Xue CB 《Bioorganic & medicinal chemistry letters》2011,21(5):1442-1446
We report the discovery of a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist (3S,4S)-N-[(1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amine (19). After evaluation in 28-day toxicology studies, compound 19 (INCB10820/PF-4178903) was selected as a clinical candidate. 相似文献
29.
Liu M Guo S Hibbert JM Jain V Singh N Wilson NO Stiles JK 《Cytokine & growth factor reviews》2011,22(3):121-130
C–X–C motif chemokine 10 (CXCL10) also known as interferon γ-induced protein 10 kDa (IP-10) or small-inducible cytokine B10 is a cytokine belonging to the CXC chemokine family. CXCL10 binds CXCR3 receptor to induce chemotaxis, apoptosis, cell growth and angiostasis. Alterations in CXCL10 expression levels have been associated with inflammatory diseases including infectious diseases, immune dysfunction and tumor development. CXCL10 is also recognized as a biomarker that predicts severity of various diseases. A review of the emerging role of CXCL10 in pathogenesis of infectious diseases revealed diverse roles of CXCL10 in disease initiation and progression. The potential utilization of CXCL10 as a therapeutic target for infectious diseases is discussed. 相似文献
30.