Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2

Casilli, Federica; Bianchini, Andrea; Gloaguen, Isabelle; Biordi, Leda; Alesse, Edoardo; Festuccia, Claudio; Cavalieri, Barbara; Strippoli, Raffaele; Cervellera, Maria Neve; Bitondo, Rosa Di; Ferretti, Elisabetta; Mainiero, Fabrizio; Bizzarri, Cinzia; Colotta, Francesco; Bertini, Riccardo

doi:10.1016/j.bcp.2004.10.007

Cited by 96 publications

(80 citation statements)

References 32 publications

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“…In fact, migration of neutrophils is influenced by DCs primarily by IL-8 (64). IL-8 is also a chemoattractant for other cell types including T cells (72). In addition, we found a significant association between IL-8 secretion and serum levels of anti-dsDNA.…”

Section: Discussionmentioning

confidence: 53%

“…In addition, we found a significant association between IL-8 secretion and serum levels of anti-dsDNA. Anti-dsDNA can enhance the release of proinflammatory cytokines, including IL-8 and TNF-␣ from mononuclear cells to augment inflammatory reactions and can polarize the immune reaction toward the Th2 pathway (72)(73)(74). Therefore, an increase in the production of this cytokine by DCs might enhance the ability to recruit cells in the glomerulus and enhance neutrophil adhesion to vascular endothelium which in turn may contribute to renal and vascular damage.…”

Section: Discussionmentioning

confidence: 99%

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Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Ding

Mehta

McCune

et al. 2006

The Journal of Immunology

129

103

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Systemic lupus erythematosus (SLE) is characterized by a systemic autoimmune response with profound and diverse T cell changes. Dendritic cells (DCs) are important orchestrators of immune responses and have an important role in the regulation of T cell function. The objective of this study was to determine whether myeloid DCs from individuals with SLE display abnormalities in phenotype and promote abnormal T cell function. Monocyte-derived DCs and freshly isolated peripheral blood myeloid DCs from lupus patients displayed an abnormal phenotype characterized by accelerated differentiation, maturation, and secretion of proinflammatory cytokines. These abnormalities were characterized by higher expression of the DC differentiation marker CD1a, the maturation markers CD86, CD80, and HLA-DR, and the proinflammatory cytokine IL-8. In addition, SLE patients displayed selective down-regulation of the maturation marker CD83 and had abnormal responses to maturation stimuli. These abnormalities have functional relevance, as SLE DCs were able to significantly increase proliferation and activation of allogeneic T cells when compared with control DCs. We conclude that myeloid DCs from SLE patients display significant changes in phenotype which promote aberrant T cell function and could contribute to the pathogenesis of SLE and organ damage.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Ding

Mehta

McCune

et al. 2006

The Journal of Immunology

129

103

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show abstract

“…In addition, it was demonstrated that the genetic disruption of CXCR2 blocked the neutrophil recruitment observed in inflammatory disease models of polynephritis and Lyme arthritis, resulting in resistance to pathology [30][31][32]. Repertaxin is a novel noncompetitive allosteric inhibitor of CXCR1 and CXCR2, and is an active blocker of neutrophil chemotaxis in humans and rodents [33][34][35]. Furthermore, it has been considered a candidate for the therapeutic prevention of tissue damage due to reperfusion injury, as demonstrated in animal models of reperfusion injury of different organs including lung, liver, brain and kidney [33,36,37].…”

Section: Discussionmentioning

confidence: 99%

Neutrophil recruitment in immunized mice depends on MIP‐2 inducing the sequential release of MIP‐1α, TNF‐α and LTB₄

et al. 2006

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Neutrophils are thought to play an important role in the tissue damage observed in various autoimmune diseases. Chemokines, cytokines and leukotrienes have recognized roles in the orchestration of neutrophil migration. We have recently shown that antigeninduced neutrophil migration into the peritoneum of immunized mice is mediated by macrophage-inflammatory protein (MIP)-1a which interacts with CCR1 and induces the sequential release of TNF-a and leukotriene B 4 (LTB 4 ). The present study investigates the role of MIP-2 and CXCR2 in the cascade of events leading to mediator generation and neutrophil influx. Antigen challenge of immunized mice induced the expression of CXCR2 and the production of KC and MIP-2 proteins. Antigen-induced neutrophil migration was inhibited by a CXCR2 receptor antagonist (repertaxin) or an anti-MIP-2 antibody, but not by an anti-KC antibody. Administration of MIP-2 promoted a dose-dependent neutrophil migration in naive mice which was inhibited by repertaxin, anti-TNF-a, anti-MIP-1a antibodies or by MK886 (leukotriene synthesis inhibitor). MIP-2 administration induced the release of MIP-1a, TNF-a and LTB 4 , and the release of the latter two was inhibited by anti-MIP-1a antibody treatment. Our studies highlight the intricate balance between mediator production and action during an immune-mediated inflammatory response and suggest a mediator cascade leading to neutrophil influx following antigen challenge of immunized mice: MIP-2 ? MIP-1a ? TNF-a ? LTB 4 .

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“…IL-8 appeared to be critical not only for tissue damage in acute inflammation but also in the well-described chemotactic effect for immune-competent cells (Baggiolini et al, 1995;Gerszten et al, 1999). It also regulates recruitment and activation of human leucocytes at sites of inflammation (Casilli et al, 2005). As yet, it is not clear whether IL-17 is involved in AA.…”

mentioning

confidence: 99%

Interleukin (IL)‐17 promotes macrophages to produce IL‐8, IL‐6 and tumour necrosis factor‐α in aplastic anaemia

Liu

et al. 2008

Br J Haematol

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SummaryAplastic anaemia (AA) is thought to be an autoimmune-mediated disease with active destruction of haematopoietic cells through a T helper type 1 (Th1) cell response. Interleukin (IL)-17 is a potent proinflammatory cytokine produced by activated memory T cells. Recent studies indicate that IL-17 might be an essential effector cytokine in the T-cell mediated autoimmune process. It can drive the production of tumour necrosis factor-a (TNF-a), IL-1 b, IL-6 and IL-8 by a variety of cells. The present study investigated the genetic and protein expression of IL-17 in patients with AA. The effect of IL-17 on IL-6 and IL-8 production by macrophages was also studied. AA patients showed an elevated expression of IL17A mRNA in bone marrow mononuclear cells and peripheral blood mononuclear cells. Higher IL-17 in bone marrow and peripheral blood plasma was also observed in AA patients compared with normal controls. IL-17 induced the production of IL-6 and IL-8 by macrophages both from patients with AA and normal controls. IL-17 stimulation also resulted in the production of TNF-a. These results suggested that elevated expression of IL-17 and IL-17-induced IL-6, IL-8 and TNF-a may be involved in the mechanisms of AA.

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Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2

Cited by 96 publications

References 32 publications

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Neutrophil recruitment in immunized mice depends on MIP‐2 inducing the sequential release of MIP‐1α, TNF‐α and LTB₄

Interleukin (IL)‐17 promotes macrophages to produce IL‐8, IL‐6 and tumour necrosis factor‐α in aplastic anaemia

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Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2

Cited by 96 publications

References 32 publications

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Neutrophil recruitment in immunized mice depends on MIP‐2 inducing the sequential release of MIP‐1α, TNF‐α and LTB4

Interleukin (IL)‐17 promotes macrophages to produce IL‐8, IL‐6 and tumour necrosis factor‐α in aplastic anaemia

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Neutrophil recruitment in immunized mice depends on MIP‐2 inducing the sequential release of MIP‐1α, TNF‐α and LTB₄