The Ligands of CXC Chemokine Receptor 3, I-TAC, Mig, and IP10, Are Natural Antagonists for CCR3

Loetscher, Pius; Pellegrino, A.; Gong, Junsong; Mattioli, Ivan; Loetscher, Marcel; Bardi, Giuseppe; Baggiolini, Marco; Clark‐Lewis, Ian

doi:10.1074/jbc.m005652200

Cited by 299 publications

(260 citation statements)

References 70 publications

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“…Transfected murine pre-B 300.19 cells stably expressing human CCR6 have been described previously [37]. RBL-2H3 cells were transfected with the human CCR6 cDNA containing expression vector (clone I.D.…”

Section: Transfected Cell Linesmentioning

confidence: 99%

β‐Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved

et al. 2007

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b-Defensins are natural peptide antibiotics whose immunomodulatory functions are poorly understood. In the present study, macrophages were found to migrate to human b-defensins (HBD)-1 to -4 using Ga i proteins as well as MAPK ERK, p38 and JNK as signal transducers. In addition, mast cells responded to HBD-1 to -4 with calcium fluxes as well as chemotaxis, which increased upon stimulation with IgE plus antigen or ionomycin. In contrast, human b-defensins were unable to induce migration of memory lymphocytes and dendritic cells (DC). Similar to HBD, the murine b-defensin (mBD)-8 mobilized macrophages and lacked the ability to recruit memory T cells. These findings were unexpected as CCR6 on memory T cells and DC has been previously observed to be a receptor for human b-defensins. In support of our findings, however, RBL-2H3 as well as 300.19 cells stably expressing CCR6 proved to be unresponsive to HBD-2 and -3. Intriguingly, our observation of a PKC-independent homologous desensitization between HBD-1 to -4 suggests a common receptor for HBD. In summary, chemoattraction of macrophages and mast cells is evolutionary conserved within the b-defensin family despite a considerable sequence variation and distinct antimicrobial activities. However, CCR6 is not a functional receptor for b-defensins.

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Section: Transfected Cell Linesmentioning

confidence: 99%

β‐Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved

et al. 2007

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“…80 The specific function of this region in hLtn, however, remains to be clarified. Due to its disordered nature, this region samples a wide range of conformations that wildly differ from the averaged NMR structure in all simulations (Fig.…”

Section: A Structural Stabilitymentioning

confidence: 99%

Effects of Temperature and Salt Concentration on the Structural Stability of Human Lymphotactin: Insights from Molecular Simulations

Formaneck

Cui

2006

J. Am. Chem. Soc.

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Extensive molecular dynamics (MD) simulations (∼ 70 ns total) with explicit solvent molecules and salt ions are carried out to probe the effects of temperature and salt concentration on the structural stability of the human Lymphotactin (hLtn). The distribution of ions near the protein surface and the stability of various structural motifs are observed to exhibit interesting dependence on the local sequence and structure. Whereas chloride association to the protein is overall enhanced as the temperature increases, the sodium distribution in the C-terminal helical region and, to a smaller degree, the chloride distribution in the same region are found higher at the lower temperature. The similar trend is also observed in non-linear Poisson-Boltzmann calculations with a temperaturedependent water dielectric constant, once conformational averaging over a series of MD snapshots is done. The unexpected temperature dependence in the ion distribution is explained based on the cancellation of association entropy for ion-sidechain pairs of opposite-charge and like-charge characters, which have positive and negative contributions, respectively. The C-terminal helix is observed to partially melt while a short • strand forms at the higher temperature with little salt dependence. The N-termal region, by contrast, develops partial helical structure at a higher salt concentration. These observed behaviors are consistent with solvent and salt screening playing an important role in stabilizing the canonical chemokine fold of hLtn.

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“…[11][12][13][14] Four subfamilies of chemokines (C, CC, CXC and CX 3 C) can be distinguished according to the arrangement of the first two cysteine residues, which may be adjacent (the 'CC' family) or separated by one or three amino acids (the 'CXC' and 'CX 3 C' families). 15,16 IFN-g induces a limited range of chemokines, 17 notably MIG (CXCL9), IP-10 (CXCL10) and I-TAC (CXCL11). 13,18 These chemokines all signal through the CXCR3 receptor; this is expressed on activated T cells, particularly Th1 cells.…”

mentioning

confidence: 99%

Interferon lambda-1 (IFN-λ1/IL-29) induces ELR− CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-γ-independent manner

et al. 2007

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Interferon lambda-1 (IFN-l1), the prototype Type-III interferon, has antiviral functions similar to those of the Type-I interferons, IFN-a and IFN-b. However, IFN-l1 is capable of signaling through almost all STAT molecules and so it is possible that it may have novel immunoregulatory functions in addition to antiviral ones. From a range of chemokines tested, IFN-l1 elevated mRNA levels of only 'Monokine induced by IFN-gamma' (MIG/CXCL9), 'IFN-gamma inducible protein-10' (IP-10/CXCL10) and 'IFN-gamma inducible T-cell a chemoattractant' (I-TAC/CXCL11) from human peripheral blood mononuclear cells. As their names suggest, these chemokines are also induced by IFN-g, the only member of the Type-II interferon family. This action of IFN-l1 did not depend on intermediate induction of IFN-g and is therefore, likely to be independent of IFN-g. Further, our results suggest that donors responded to IFN-l1 stimulation either 'early' or 'late'. Overall the action of IFN-l1 was similar to that previously reported for IFN-g and may invite more detailed investigation of the role of IFN-l1 at the innate/adaptive interface.

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The Ligands of CXC Chemokine Receptor 3, I-TAC, Mig, and IP10, Are Natural Antagonists for CCR3

Cited by 299 publications

References 70 publications

β‐Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved

β‐Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved

Effects of Temperature and Salt Concentration on the Structural Stability of Human Lymphotactin: Insights from Molecular Simulations

Interferon lambda-1 (IFN-λ1/IL-29) induces ELR− CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-γ-independent manner

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