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Several Chemokines (several + chemokine)
Selected AbstractsThe antimicrobial activity of CCL28 is dependent on C-terminal positively-charged amino acidsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2010Bin Liu Abstract Several chemokines have been shown to act as antimicrobial proteins, suggesting a direct contribution to innate immune protection. Based on the study of defensins and other antimicrobial peptides, it has been proposed that cationic amino acids in these proteins play a key role in their antimicrobial activity. The primary structure requirements necessary for the antimicrobial activity of chemokines, however, have not yet been elucidated. Using mouse CCL28, we have identified a C-terminal region of highly-charged amino acids (RKDRK) that is essential to the antimicrobial activity of the murine chemokine. Additionally, other positively-charged amino acids in the C-terminus of the protein contribute to the observed antimicrobial effect. Charge reversal and deletion mutations support our hypothesis that C-terminal positively-charged amino acids are essential for the antimicrobial activity of CCL28. Results also demonstrate that although the C-terminal region of the chemokine is essential, it is not sufficient for full antimicrobial activity of CCL28. [source] Spatiotemporal expression of chemokines and chemokine receptors in experimental anti-myeloperoxidase antibody-mediated glomerulonephritisCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2009B. S. Van Der Veen Summary Myeloperoxidase (MPO)-anti-neutrophil cytoplasmic autoantibody (ANCA)-associated necrotizing crescentic glomerulonephritis (NCGN) is characterized by abundant leucocyte infiltration. Chemokines are chemotactic cytokines involved in receptor-mediated recruitment of leucocytes. Our objective was to analyse spatiotemporal gene expression of chemokines and chemokine receptors in anti-MPO-mediated NCGN, to find potential targets for intervening with leucocyte influx. NCGN was induced in mice by co-administration of anti-MPO immunoglobulin (Ig)G and lipopolysaccharide. mRNA expression levels of chemokines and chemokine receptors were analysed in whole kidney lysates as well as in laser microdissected glomeruli and tubulo-interstitial tissue 1 and 7 day(s) after NCGN induction. Several chemokines and chemokine receptors were induced or up-regulated in anti-MPO-mediated NCGN, both on day 1 (chemokines CCL3, 5; CXCL2, 5, 13; receptor CXCR2) and on day 7 (chemokines CCL2, 5, 7, 8, 17, 20; CXCL1, 2, 5, 10; CX3CL1; receptors CCR2, 8; CX3CR1). The expression levels of most chemokines and receptors were higher in glomeruli than in the tubulo-interstitium. Because of the temporal induction of CXCR2 on day 1, we hypothesized CXCR2 as a potential target for treatment in anti-MPO-induced NCGN. Inhibition of CXCR2 using a goat-anti-CXCR2 serum prior to NCGN induction increased glomerular neutrophil influx but did not affect crescent formation and albuminuria. In conclusion, expression levels of various chemokines and chemokine receptors were increased in anti-MPO NCGN, and expressed particularly in glomeruli. These chemokines and receptors may serve as potential targets for treatment. Inhibition of a single target, CXCR2, did not attenuate anti-MPO NCGN. Combinatorial interventions may be necessary to avoid redundancy. [source] CCL22-induced responses are powerfully enhanced by synergy inducing chemokines via CCR4: evidence for the involvement of first ,-strand of chemokineEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2005Silvia Sebastiani Abstract In an attempt to clarify how cells integrate the signals provided by multiple chemokines expressed during inflammation, we have uncovered a novel mechanism regulating leukocyte trafficking. Our data indicate that the concomitant exposure to CCR4 agonists and CXCL10/IP-10 strongly enhances the chemotactic response of human T lymphocytes. This enhancement is synergistic rather than additive and occurs via CCR4 since it persists after CXCR3 blockade. Besides chemotaxis, other cellular responses are enhanced upon stimulation of CCR4-transfected cells with CCL22/MDC plus CXCL10. Several other chemokines in addition to CXCL10 were able to increase CCL22-mediated chemotaxis. The first ,-strand of the chemokine structure is highly and specifically implicated in this phenomenon, as established using synergy-inducing and non-synergy-inducing chimeric chemokines. As shown in situ for skin from atopic and allergic contact dermatitis patients, this organ becomes the ideal environment in which skin-homing CCR4+ T lymphocytes can accumulate under the stimulus offered by CCR4 agonists, together with the synergistic chemokines that are concomitantly expressed. Overall, our results indicate that chemokine-induced synergism strengthens leukocyte recruitment towards tissues co-expressing several chemokines. [source] A review on the interactions between gut microbiota and innate immunity of fishFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2008Geovanny D. Gómez Abstract Although fish immunology has progressed in the last few years, the contribution of the normal endogenous microbiota to the overall health status has been so far underestimated. In this context, the establishment of a normal or protective microbiota constitutes a key component to maintain good health, through competitive exclusion mechanisms, and has implications for the development and maturation of the immune system. The normal microbiota influences the innate immune system, which is of vital importance for the disease resistance of fish and is divided into physical barriers, humoral and cellular components. Innate humoral parameters include antimicrobial peptides, lysozyme, complement components, transferrin, pentraxins, lectins, antiproteases and natural antibodies, whereas nonspecific cytotoxic cells and phagocytes (monocytes/macrophages and neutrophils) constitute innate cellular immune effectors. Cytokines are an integral component of the adaptive and innate immune response, particularly IL-1,, interferon, tumor necrosis factor-,, transforming growth factor-, and several chemokines regulate innate immunity. This review covers the innate immune mechanisms of protection against pathogens, in relation with the installation and composition of the normal endogenous microbiota in fish and its role on health. Knowledge of such interaction may offer novel and useful means designing adequate therapeutic strategies for disease prevention and treatment. [source] The protein kinase C agonist PEP005 increases NF-,B expression, induces differentiation and increases constitutive chemokine release by primary acute myeloid leukaemia cellsBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2009Astrid Marta Olsnes Summary Acute myeloid leukaemia (AML) cells show constitutive release of several chemokines that occurs in three major clusters: (I) chemokine (C-C motif) ligand (CCL)2,4/chemokine (C-X-C motif) ligand (CXCL)1/8, (II) CCL5/CXCL9,11 and (III) CCL13/17/22/24/CXCL5. Ingenol-3-angelate (PEP005) is an activator of protein kinase C and has antileukaemic and immunostimulatory effects in AML. We investigated primary AML cells derived from 35 unselected patients and determined that PEP005 caused a dose-dependent increase in the release of chemokines from clusters I and II, including several T cell chemotactic chemokines. The release of granulocyte-macrophage colony-stimulating factor and hepatocyte growth factor was also increased. CCL2,4/CXCL1/8 release correlated with nuclear factor (NF)-,B expression in untreated AML cells, and PEP005-induced chemokine production was associated with further increases in the expression of the NF-,B subunits p50, p52 and p65. Increased DNA binding of NF-,B was observed during exposure to PEP005, and the specific NF-,B inhibitor BMS-345541 reduced constitutive chemokine release even in the presence of PEP005. Finally, PEP005 decreased expression of stem cell markers (CD117, CXCR4) and increased lineage-associated CD11b and CD14 expression. To conclude, PEP005 has a unique functional pharmacological profile in human AML. Previous studies have described proapoptotic and T cell stimulatory effects and the present study describes additional T cell chemotactic and differentiation-inducing effects. [source] | ||||||||||