O. M. Zack Howard

Center for Cancer Research

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Co-Authors

Joost J. Oppenheim

Frederick National Laboratory for Cancer Research

Xin Chen

University of Macau

De Yang

Frederick National Laboratory for Cancer Research

William L. Farrar

National Cancer Institute

Wanghua Gong

Osaka University

Hui Dong

Fujian Academy of Agricultural Sciences

Ji Ming Wang

Frederick National Laboratory for Cancer Research

Jim A. Turpin

Office of AIDS Research

Keqiang Chen

China University of Geosciences (Beijing)

Poonam Tewary

Frederick National Laboratory for Cancer Research

Cooperative Institutions

Carnegie Corporation of New York

375

Institute of International Education

373

Ford Foundation

371

National Cancer Institute

189

National Institutes of Health

167

Center for Cancer Research

122

Frederick National Laboratory for Cancer Research

116

Science Applications International Corporation (United States)

The University of Texas MD Anderson Cancer Center

Harvard University

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Chemotactic Activity of S100A7 (Psoriasin) Is Mediated by the Receptor for Advanced Glycation End Products and Potentiates Inflammation with Highly Homologous but Functionally Distinct S100A15

The Journal of Immunology (2008)

Ronald Wolf O. M. Zack Howard Huifang Dong Christopher Voscopoulos Karen M. Boeshans

Abstract Human S100A7 (psoriasin) is overexpressed in inflammatory diseases. The recently discovered, co-evolved hS100A15 is almost identical in sequence and up-regulated with hS100A7 during cutaneous inflammation. The functional role of these closely related proteins for inflammation remains undefined. By generating specific Abs, we demonstrate that hS100A7 and hS100A15 proteins are differentially expressed by specific cell types in the skin. Although highly homologous, both proteins are chemoattractants with distinct chemotactic activity for leukocyte subsets. We define RAGE (receptor for advanced glycation end products) as the hS100A7 receptor, whereas hS100A15 functions through a Gi protein-coupled receptor. hS100A7-RAGE binding, signaling, and chemotaxis are zinc-dependent in vitro, reflecting the previously reported zinc-mediated changes in the hS100A7 dimer structure. When combined, hS100A7 and hS100A15 potentiate inflammation in vivo. Thus, proinflammatory synergism in disease may be driven by the diverse biology of these almost identical proteins that have just recently evolved. The identified S100A7 interaction with RAGE may provide a novel therapeutic target for inflammation.

RAGE

Proinflammatory cytokine

10.4049/jimmunol.181.2.1499

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Citations (164)

Data from Transactivation of the Epidermal Growth Factor Receptor by Formylpeptide Receptor Exacerbates the Malignant Behavior of Human Glioblastoma Cells

Jian Huang Jinyue Hu Xiu‐Wu Bian Keqiang Chen Wanghua Gong

<div>Abstract<p>The G protein-coupled formylpeptide receptor (FPR), which mediates leukocyte migration in response to bacterial and host-derived chemotactic peptides, promotes the chemotaxis, survival, and tumorigenesis of highly malignant human glioblastoma cells. Because glioblastoma cells may also express other receptors for growth signals, such as the epidermal growth factor (EGF) receptor (EGFR), we investigated the role of EGFR in the signaling cascade of FPR and how two receptors cross-talk to exacerbate tumor growth. We found that <i>N</i>-formyl-methionyl-leucyl-phenylalanine, an FPR agonist peptide, rapidly induced EGFR phosphorylation at tyrosine residue (Tyr) 992, but not residues 846, 1068, or 1173, in glioblastoma cells, whereas all these residues were phosphorylated after only EGF treatment. The FPR agonist-induced EGFR phosphorylation in tumor cells was dependent on the presence of FPR as well as Gαi proteins, and was controlled by Src tyrosine kinase. The transactivation of EGFR contributes to the biological function of FPR in glioblastoma cells because inhibition of EGFR phosphorylation significantly reduced FPR agonist-induced tumor cell chemotaxis and proliferation. Furthermore, depletion of both FPR and EGFR by short interference RNA abolished the tumorigenesis of the glioblastoma cells. Our study indicates that the glioblastoma-promoting activity of FPR is mediated in part by transactivation of EGFR and the cross-talk between two receptors exacerbates the malignant phenotype of tumor cells. Thus, targeting both receptors may yield antiglioblastoma agents superior to those targeting one of them. [Cancer Res 2007;67(12):5906–13]</p></div>

10.1158/0008-5472.c.6495488.v1

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Chemokine receptors on dendritic cells promote autoimmune

De Yang Arya Biragyn O. M. Zack Howard Paul H. Plötz Joost J. Oppenheim

CCL25

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In vitro generated Th17 cells support the expansion and phenotypic stability of CD4+Foxp3+ regulatory T cells in vivo

Cytokine (2013)

Qiong Zhou Ya Hu O. M. Zack Howard Joost J. Oppenheim Xin Chen

10.1016/j.cyto.2013.09.008

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Citations (21)

Interleukin-2 induces tyrosine phosphorylation of the vav proto-oncogene product in human T cells: lack of requirement for the tyrosine kinase lck

Biochemical Journal (1993)

Gerald A. Evans O. M. Zack Howard Rebecca A. Erwin William L. Farrar

The haematopoietic protein, p95vav, has been shown to be a tyrosine kinase substrate and to have tyrosine kinase-modulated guanine-nucleotide-releasing-factor activity. This implies a function in the control of ras or ras-like proteins. Because ras activation has been shown to be a downstream event following stimulation of the interleukin-2 (IL-2) receptor, we investigated the possibility that vav was involved in IL-2 signal transduction pathways, using human T cells as a model. We found rapid tyrosine phosphorylation of vav in response to IL-2 within 1 min, with maximum increase of phosphorylation of 5-fold occurring by 5 min after treatment in normal human T cells. IL-2 stimulation of the human T-cell line YT and a subclone of the YT cell line (YTlck-) that does not express message for the src-family kinase p56lck also results in a rapid rate of tyrosine phosphorylation of vav of more than 5-fold by 5 min. These results suggest that vav may play an important role in IL-2-stimulated signal transduction and that there is not a strict requirement for the tyrosine kinase p56lck.

10.1042/bj2940339

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Citations (60)

Small molecule inhibitor of HIV-1 cell fusion blocks chemokine receptor-mediated function

Journal of Leukocyte Biology (1998)

O. M. Zack Howard Thomas Korte Nadya I. Tarasova Michael Grimm Jim A. Turpin

Abstract The intersection of the HIV and the chemokine fields began with the observation that HIV entry into cells could be blocked by certain chemokines. Subsequent work showed that HIV entry is dependent on the presence of specific chemokine receptors. These observations led us to evaluate a series of compounds, ureido analogs of distamycin previously reported to block HIV entry into cells in vitro, for chemokine antagonist activity. One of the distamycin analogs, 2,2′[4,4′-[[aminocarbonyl]amino]bis[N,4′-di[pyrrole-2-carboxamide-1,1′-dimethyl]]-6,8 napthalenedisulfonic acid] hexasodium salt (NSC 651016), is shown here to inhibit syncytia formation and cell fusion. Mechanistic studies showed that this inhibition was not due to conformational changes in gp120-gp41 induced by target cell CD4 and chemokine co-receptor and was therefore not due to interference with binding of HIV-1. Additional mechanistic studies demonstrated that NSC 651016 inhibited chemokine binding to specific chemokine receptors, induced CXCR4 and CCR5 receptor internalization, and inhibited chemokine-induced chemotaxis by macrophage inflammatory protein (MIP)-1α, MIP-1β, RANTES, and stromal-derived factor-1α but not monocyte chemotactic protein-1. Thus, we describe a novel compound that inhibits in vivo replication of HIV-1 by down-regulation of co-receptors. These data lead us to propose that NSC 651016 may have in vivo anti-inflammatory activity. J. Leukoc. Biol. 64: 6–13; 1998.

XCL2

CCR5 receptor antagonist

CCR1

Chemokine receptor CCR5

CCL21

CXCL14

CCR2

CCL5

CXCL2

CC chemokine receptors

10.1002/jlb.64.1.6

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Citations (48)

LEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8

Blood (2000)

O. M. Zack Howard Hui Dong Aiko‐Konno Shirakawa Joost J. Oppenheim

Polyclonal antibodies

CCR1

HEK 293 cells

10.1182/blood.v96.3.840.015k32_840_845

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Citations (8)

IKKalpha is critical for the maintenance of a normal pool of regulatory T cells and for the expansion of both regulatory and effector T cells

Xin Chen Jami Willette‐Brown Xueqiang Wu O. M. Zack Howard Yinling Hu

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Inhibition of the Expression and Function of Chemokine Receptors on Human CD4+ Leukocytes by HIV-1 Envelope Protein gp120

KARGER eBooks (1999)

Shao Bo Su Hirotsugu Ueda O. M. Zack Howard Michael Grimm Wanghua Gong

Envelope (radar)

Chemokine receptor CCR5

CCL25

10.1159/000058731

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Citations (15)

Inducible NOS-induced chloride intracellular channel 4 (CLIC4) nuclear translocation regulates macrophage deactivation

Proceedings of the National Academy of Sciences (2012)

Mariam Malik Kasey Jividen V. C. Padmakumar Christophe Cataisson Luowei Li

Nuclear translocation of cytosolic CLIC4 is an essential feature of its proapoptotic and prodifferentiation functions. Here we demonstrate that CLIC4 is induced concurrently with inducible nitric oxide synthase (iNOS) and S-nitrosylated in proinflammatory peritoneal macrophages. Chemical inhibition or genetic ablation of iNOS inhibits S-nitrosylation and nuclear translocation of CLIC4. In macrophages, iNOS-induced nuclear CLIC4 coincides with the pro- to anti-inflammatory transition of the cells because IL-1β and CXCL1 mRNA remain elevated in CLIC4 and iNOS knockout macrophages at late time points, whereas TNFα mRNA is elevated only in the iNOS knockout macrophages. Active IL-1β remains elevated in CLIC4 knockout macrophages and in macrophages in which CLIC4 nuclear translocation is prevented by the NOS inhibitor l -NAME. Moreover, overexpression of nuclear-targeted CLIC4 down-regulates IL-1β in stimulated macrophages. In mice, genetically null for CLIC4, the number of phagocytosing macrophages stimulated by LPS is reduced. Thus, iNOS-induced nuclear CLIC4 is an essential part of the macrophage deactivation program.

Proinflammatory cytokine

10.1073/pnas.1201351109

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Citations (56)