scholarly journals Defective tumor necrosis factor release from Crohnʼs disease macrophages in response to toll-like receptor activation: Relationship to phenotype and genome-wide association susceptibility loci

2012 ◽  
Vol 18 (11) ◽  
pp. 2120-2127 ◽  
Author(s):  
Gavin W. Sewell ◽  
Farooq Z. Rahman ◽  
Adam P. Levine ◽  
Luke Jostins ◽  
Philip J. Smith ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Receptor Activation ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Toll Like Receptor ◽  
Genome Wide ◽  
Necrosis Factor ◽  
Factor Release

scholarly journals Human Immunodeficiency Virus Infection Alters Tumor Necrosis Factor Alpha Production via Toll-Like Receptor-Dependent Pathways in Alveolar Macrophages and U1 Cells

2008 ◽  
Vol 82 (16) ◽  
pp. 7790-7798 ◽  
Author(s):  
Marlynne Q. Nicol ◽  
Jean-Marie Mathys ◽  
Albertina Pereira ◽  
Kevin Ollington ◽  
Michael H. Ieong ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Innate Immune ◽  
Hiv Positive ◽  
Toll Like Receptor ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Human immunodeficiency virus (HIV)-positive persons are predisposed to pulmonary infections, even after receiving effective highly active antiretroviral therapy. The reasons for this are unclear but may involve changes in innate immune function. HIV type 1 infection of macrophages impairs effector functions, including cytokine production. We observed decreased constitutive tumor necrosis factor alpha (TNF-α) concentrations and increased soluble tumor necrosis factor receptor type II (sTNFRII) in bronchoalveolar lavage fluid samples from HIV-positive subjects compared to healthy controls. Moreover, net proinflammatory TNF-α activity, as measured by the TNF-α/sTNFRII ratio, decreased as HIV-related disease progressed, as manifested by decreasing CD4 cell count and increasing HIV RNA (viral load). Since TNF-α is an important component of the innate immune system and is produced upon activation of Toll-like receptor (TLR) pathways, we hypothesized that the mechanism associated with deficient TNF-α production in the lung involved altered TLR expression or a deficit in the TLR signaling cascade. We found decreased Toll-like receptor 1 (TLR1) and TLR4 surface expression in HIV-infected U1 monocytic cells compared to the uninfected parental U937 cell line and decreased TLR message in alveolar macrophages (AMs) from HIV-positive subjects. In addition, stimulation with TLR1/2 ligand (Pam3Cys) or TLR4 ligand (lipopolysaccharide) resulted in decreased intracellular phosphorylated extracellular signal-regulated kinase and subsequent decreased transcription and expression of TNF-α in U1 cells compared to U937 cells. AMs from HIV-positive subjects also showed decreased TNF-α production in response to these TLR2 and TLR4 ligands. We postulate that HIV infection alters expression of TLRs with subsequent changes in mitogen-activated protein kinase signaling and cytokine production that ultimately leads to deficiencies of innate immune responses that predispose HIV-positive subjects to infection.

Toll-like Receptor-mediated Tumor Necrosis Factor and Interleukin-10 Production Differ during Systemic Inflammation

2003 ◽  
Vol 168 (2) ◽  
pp. 158-164 ◽  
Author(s):  
Minou Adib-Conquy ◽  
Pierre Moine ◽  
Karim Asehnoune ◽  
Alain Edouard ◽  
Terje Espevik ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Systemic Inflammation ◽  
Tumor Necrosis ◽  
Interleukin 10 ◽  
Toll Like Receptor ◽  
Necrosis Factor
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