Recent work conducted in our laboratory has been directed towards understanding the role of TNF alpha in stimulating the synthesis of two macrophage gene products, namely IGF-1, a growth factor implicated in wound repair and fibrosis, and complement component factor B (Bf), an alternative pathway complement component. The expression of these proteins is induced by hyaluronic acid and poly (I:C), respectively, although TNF alpha plays a requisite role in the expression of both proteins. The objective of this study was to determine the mechanism governing the dichotomy in the expression of IGF-1 and Bf by TNF alpha. First, we questioned if the diversity in IGF-1 and Bf synthesis was regulated at the level of TNF receptor usage. Second, based on earlier findings that IFNs contribute to the initiation of Bf expression, we determined if IFNs modulate the response of macrophages to TNF alpha. Our data show that differences in TNF receptor usage cannot fully explain the dichotomy in the expression of IGF-1 and Bf. However, prior exposure to IFN-beta or IFN-gamma was found to be a dominant factor controlling the expression of these proteins, suppressing IGF-1, and enhancing Bf. These findings indicate that IFNs mediate a functional "switch" in the response of macrophages to TNF alpha and suggest that the pattern of cytokine expression by diverse macrophage stimuli is an important determinant of the eventual responses of macrophages to TNF alpha.
F R Lake, P W Noble, P M Henson, D W Riches
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2021 | |
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Interleukin-12p35 knockout promotes macrophage differentiation, aggravates vascular dysfunction, and elevates blood pressure in angiotensin II-infused mice
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TNF-α Accelerates the Resolution of Established Pulmonary Fibrosis in Mice by Targeting Pro-Fibrotic Lung Macrophages
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Macrophage Differentiation and Polarization via Phosphatidylinositol 3-Kinase/Akt–ERK Signaling Pathway Conferred by Serum Amyloid P Component
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Evidence of a role for lactadherin in Alzheimer's disease
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2007 | |
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Inhibition of Macrophage Nuclear Factor-κB Leads to a Dominant Anti-Inflammatory Phenotype that Attenuates Glomerular Inflammation in Vivo
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The American Journal of Pathology | 2005 |
Immunoendocrinology in Health and Disease
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Immunoendocrinology in Health and Disease | 2004 |
IL-4-induced macrophage-derived IGF-I protects myofibroblasts from apoptosis following growth factor withdrawal
MW Wynes, SK Frankel, DW Riches |
Journal of leukocyte biology | 2004 |
Induction of Macrophage Insulin-Like Growth Factor-I Expression by the Th2 Cytokines IL-4 and IL-13
MW Wynes, DW Riches |
Journal of immunology (Baltimore, Md. : 1950) | 2003 |
Heterogeneity of macrophage activation in anti-Thy-1.1 nephritis
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The American Journal of Pathology | 2003 |
The Role of Circulating IGF-I: Lessons from Human and Animal Models
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Alpha/beta interferon impairs the ability of human macrophages to control growth of Mycobacterium bovis BCG
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Activated macrophages for treating skin ulceration: gene expression in human monocytes after hypo-osmotic shock
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Constitutive Retinal CD200 Expression Regulates Resident Microglia and Activation State of Inflammatory Cells during Experimental Autoimmune Uveoretinitis
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The American Journal of Pathology | 2002 |
Complement Factor B Gene Regulation: Synergistic Effects of TNF-α and IFN-γ in Macrophages
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Journal of immunology (Baltimore, Md. : 1950) | 2002 |
Lipoxins, Aspirin-Triggered Epi-Lipoxins, Lipoxin Stable Analogues, and the Resolution of Inflammation: Stimulation of Macrophage Phagocytosis of Apoptotic Neutrophils In Vivo
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Journal of the American Society of Nephrology : JASN | 2002 |
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Clinical & Experimental Immunology | 2001 |
Characterization of IFN-γ regulation of the complement factor B gene in macrophages
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European Journal of Immunology | 2001 |
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Tumor-Infiltrating Macrophages Induce Apoptosis in Activated CD8 + T Cells by a Mechanism Requiring Cell Contact and Mediated by Both the Cell-Associated Form of TNF and Nitric Oxide
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Macrophages from Inflamed but Not Normal Glomeruli Are Unresponsive to Anti-Inflammatory Cytokines
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The American Journal of Pathology | 2000 |
Regulation of the differentiation and function of osteoclasts
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The Journal of Pathology | 2000 |
Interferon-γ Directly Inhibits TRANCE-Induced Osteoclastogenesis
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Biochemical and Biophysical Research Communications | 2000 |
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Physiology & Behavior | 2000 |
TGF-β 1 and IFN-γ Direct Macrophage Activation by TNF-α to Osteoclastic or Cytocidal Phenotype
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Kidney International | 1999 |
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Nephrology Dialysis Transplantation | 1999 |
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1999 | |
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Blood | 1999 |
Potential Role of the JNK/SAPK Signal Transduction Pathway in the Induction of iNOS by TNF-α
ED Chan, DW Riches |
Biochemical and Biophysical Research Communications | 1998 |
Cooperative signaling by tumor necrosis factor receptors CD120a (p55) and CD120b (p75) in the expression of nitric oxide and inducible nitric oxide synthase by mouse macrophages
DW Riches, ED Chan, EA Zahradka, BW Winston, LK Remigio, FR Lake |
The Journal of biological chemistry | 1998 |
Preferential activation of the p46 isoform of JNK/SAPK in mouse macrophages by TNF alpha
ED Chan, BW Winston, MB Jarpe, MW Wynes, DW Riches |
Proceedings of the National Academy of Sciences | 1997 |
Preferential activation of the p46 isoform of JNK/SAPK in mouse macrophages by TNF
ED Chan, BW Winston, MB Jarpe, MW Wynes, DW Riches |
Proceedings of the National Academy of Sciences | 1997 |
Isolation from Fetal Bovine Serum of a Fragment b of Complement Factor B-like Protein Improving a Long-Term Survival of Human Endothelial Cells
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Archives of Biochemistry and Biophysics | 1997 |
Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44
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Journal of Clinical Investigation | 1996 |
Insulin-like growth factors and inflammatory bowel disease
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Bailliere's Clinical Gastroenterology | 1996 |
Tumor necrosis factor-alpha modulates monocyte/macrophage apoprotein E gene expression
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Journal of Clinical Investigation | 1995 |
Tumor necrosis factor alpha rapidly activates the mitogen-activated protein kinase (MAPK) cascade in a MAPK kinase kinase-dependent, c-Raf-1-independent fashion in mouse macrophages
BW Winston, CA Lange-Carter, AM Gardner, GL Johnson, DW Riches |
Proceedings of the National Academy of Sciences | 1995 |
Signalling heterogeneity as a contributing factor in macrophage functional diversity
DW Riches |
Seminars in Cell Biology | 1995 |
Preferential Involvement of MEK1 in the Tumor Necrosis Factor-α-induced Activation of p42 mapk/erk2 in Mouse Macrophages
BW Winston, LK Remigio, DW Riches |
The Journal of biological chemistry | 1995 |
The Molecular and Cellular Biology of Wound Repair
RA Clark, PM Henson |
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