Tumor necrosis factor, interferon-τ, interleukin-1 and 8, induce neuthrophil migration “in vivo” by indirect mechanisms

1990 ◽  
Vol 183 (6) ◽  
pp. 2245-2246 ◽  
Author(s):  
F.Q. Cunha ◽  
R.A. Ribeiro ◽  
L.H. Faccioli ◽  
G.E.P. Souza ◽  
S.H. Ferreira
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Necrosis Factor

scholarly journals Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1.

1995 ◽  
Vol 181 (6) ◽  
pp. 2237-2247 ◽  
Author(s):  
J A Roake ◽  
A S Rao ◽  
P J Morris ◽  
C P Larsen ◽  
D F Hankins ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Renal Medulla ◽  
Cell Loss ◽  
Systemic Administration ◽  
Lymphoid Tissues ◽  
Obvious Effect ◽  
Necrosis Factor

Dendritic cells (DC) in nonlymphoid organs can internalize and process foreign antigens before migrating to secondary lymphoid tissues to initiate primary immune responses. However, there is little information on which stimuli promote migration of DC from the tissues. Systemic administration of lipopolysaccharide (LPS), which induces in vivo production of cytokines, led to a reduction in the numbers of major histocompatibility complex class II-positive (Ia+) leukocytes in mouse hearts and kidneys: > 95% of DC were depleted 1-3 d after injection of 50 micrograms LPS. Several lines of evidence indicated that this response was due to migration of DC rather than loss of Ia expression or cytotoxic effects. In skin of treated mice, the number of Ia+ epidermal Langerhans' cells (LC) was reduced, and "cords" of Ia+ leukocytes became evident in the dermis. The latter cells expressed little NLDC145 and may have originated from recruited or resident DC progenitors. Systemic administration of recombinant tumor necrosis factor (rhTNF)-alpha resulted in a decrease in numbers of Ia+ cells in heart and kidney and of epidermal LC, and it also induced dermal cords. Administration of a rh-interleukin (IL)-1 resulted in a decrease in Ia+ cells only in renal medulla, appeared to activate a subset of epidermal LC, and induced dermal cords. Similar microgram doses of rhIL-2 had no obvious effect. Treatment with a neutralizing anti-TNF antiserum before LPS administration inhibited the depletion of LC from skin but not from heart or kidney. Therefore, TNF-alpha and IL-1 alpha may promote DC migration from nonlymphoid tissues and may have differential effects on different DC populations, but it is unclear whether they act on DC directly or indirectly (e.g., via other cytokines).

scholarly journals Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation.

1993 ◽  
Vol 13 (6) ◽  
pp. 3301-3310 ◽  
Author(s):  
A A Beg ◽  
T S Finco ◽  
P V Nantermet ◽  
A S Baldwin
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Activation Process ◽  
Nf Kappa B ◽  
I Kappa B Alpha ◽  
Subsequent Loss ◽  
Autoregulatory Mechanism ◽  
Necrosis Factor

Nuclear factor kappa B (NF-kappa B) is a critical regulator of several genes which are involved in immune and inflammation responses. NF-kappa B, consisting of a 50-kDa protein (p50) and a 65-kDa protein (p65), is bound to a cytoplasmic retention protein called I kappa B. Stimulation of cells with a variety of inducers, including cytokines such as tumor necrosis factor and interleukin-1, leads to the activation and the translocation of p50/65 NF-kappa B into the nucleus. However, the in vivo mechanism of the activation process remains unknown. Here, we provide the first evidence that the in vivo mechanism of NF-kappa B activation is through the phosphorylation and subsequent loss of its inhibitor, I kappa B alpha. We also show that both I kappa B alpha loss and NF-kappa B activation are inhibited in the presence of antioxidants, demonstrating that the loss of I kappa B alpha is a prerequisite for NF-kappa B activation. Finally, we demonstrate that I kappa B alpha is rapidly resynthesized after loss, indicating that an autoregulatory mechanism is involved in the regulation of NF-kappa B function. We propose a mechanism for the activation of NF-kappa B through the modification and loss of I kappa B alpha, thereby establishing its role as a mediator of NF-kappa B activation.

scholarly journals Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes.

1991 ◽  
Vol 173 (3) ◽  
pp. 699-703 ◽  
Author(s):  
E P Sampaio ◽  
E N Sarno ◽  
R Galilly ◽  
Z A Cohn ◽  
G Kaplan
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Human Monocyte ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Thalidomide selectively inhibits the production of human monocyte tumor necrosis factor alpha (TNF-alpha) when these cells are triggered with lipopolysaccharide and other agonists in culture. 40% inhibition occurs at the clinically achievable dose of the drug of 1 micrograms/ml. In contrast, the amount of total protein and individual proteins labeled with [35S]methionine and expressed on SDS-PAGE are not influenced. The amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony-stimulating factor produced by monocytes remain unaltered. The selectivity of this drug may be useful in determining the role of TNF-alpha in vivo and modulating its toxic effects in a clinical setting.

Characterization of E-selectin expression in vivo with use of a radiolabeled monoclonal antibody

1994 ◽  
Vol 266 (1) ◽  
pp. H279-H290 ◽  
Author(s):  
E. T. M. Keelan ◽  
S. T. Licence ◽  
A. M. Peters ◽  
R. M. Binns ◽  
D. O. Haskard
Keyword(s):  
Monoclonal Antibody ◽  
Tumor Necrosis Factor ◽  
Phorbol Myristate Acetate ◽  
Tumor Necrosis ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Myristate Acetate ◽  
Necrosis Factor

We have studied endothelial luminal surface expression of E-selectin in vivo in the pig. Intravenous interleukin-1 (IL-1, 5-μg/kg bolus ± 50-ng·kg-1·min-1 infusion for 2 h) induced E-selectin expression in many organs, as shown by immunostaining and selective clearance of intravenous 111In- or 99mTc-labeled anti-E-selectin monoclonal antibody MAb 1.2B6) compared with radiolabeled immunoglobulin G1 control. Specific clearance of MAb 1.2B6 commenced 30­45 min after intravenous IL-1. Skin sites injected with IL-1, tumor necrosis factor, phytohemagglutinin, or phorbol myristate acetate at various times (45 min­24 h) before exsanguination showed specific accumulation of MAb 1.2B6 when 99mTc-MAb 1.2B6 and 111In-control immunoglobulin G1 were injected intravenously 10 min before exsanguination. This was maximal in 2-h IL-1 and tumor necrosis factor lesions and after 9 h in phytohemagglutinin and phorbol myristate acetate lesions. This novel approach has allowed us to quantify changes in vascular luminal expression of E-selectin in models of inflammation involving systemic and localized endothelial cell activation and has considerable potential for analyzing these changes in relation to leukocyte traffic and other manifestations of inflammatory responses in vivo. endothelium; inflammation; radioimmunodetection Submitted on February 25, 1993 Accepted on June 23, 1993

Chlorpromazine protection against interleukin-1 and tumor necrosis factor-mediated activities in vivo

1991 ◽  
Vol 13 (8) ◽  
pp. 1085-1090 ◽  
Author(s):  
Riccardo Bertini ◽  
Manuela Mengozzi ◽  
Marina Bianchi ◽  
Jean D. Sipe ◽  
Pietro Ghezzi
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Necrosis Factor

scholarly journals Inhibition of Tumor Necrosis Factor Alpha-Induced NF-κB Activation by the Adenovirus E3-10.4/14.5K Complex

2002 ◽  
Vol 76 (11) ◽  
pp. 5515-5521 ◽  
Author(s):  
Joshua M. Friedman ◽  
Marshall S. Horwitz
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
E3 Region ◽  
Necrosis Factor

ABSTRACT Recombinant adenoviruses (Ads) are useful tools in gene transfer because they are able to infect a wide variety of tissues and cell types and do not require a replicating target cell. However, transgene expression is only transient due to host innate and acquired immune responses to the virus. Most recombinant Ads have deletions of early region 3 (E3) genes, allowing more space for insertion of the transgene. Although the E3 region is not necessary for infection, it has been observed that these “nonessential” genes have immunomodulatory properties. We demonstrate here that the E3 region of Ad inhibits the activation of NF-κB induced by tumor necrosis factor alpha (TNF-α) and interleukin-1. Ad E3 is able to prevent NF-κB from entering the nucleus, where it is normally active. Ad E3 also appears to function by preventing the activation of the kinase complex, IKK, which is responsible for phosphorylation of IκB that retains NF-κB in the cytoplasm in an inactive state. The prevention of NF-κB activation has been mapped to a complex of two of the seven E3 products, E3-10.4K and E3-14.5K (RIDα/β). These and other studies indicate that, by using Ad vectors containing the E3 region, it may be possible to reduce the harmful proinflammatory effects of TNF-α and other cytokines that compromise the use of Ad gene therapy vectors in vivo.

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