Linked Life Data

18524817

Source:http://linkedlifedata.com/resource/pubmed/id/18524817

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2008-7-29
pubmed:abstractText
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-alpha) 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-alpha activity, as measured by the TNF-alpha/sTNFRII ratio, decreased as HIV-related disease progressed, as manifested by decreasing CD4 cell count and increasing HIV RNA (viral load). Since TNF-alpha 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-alpha 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 (Pam(3)Cys) or TLR4 ligand (lipopolysaccharide) resulted in decreased intracellular phosphorylated extracellular signal-regulated kinase and subsequent decreased transcription and expression of TNF-alpha in U1 cells compared to U937 cells. AMs from HIV-positive subjects also showed decreased TNF-alpha 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.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-10232388, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-10364338, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-10631206, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-10857863, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-10920188, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-11062499, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-11095740, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-11923281, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-11964313, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-11985485, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-11994482, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-12077222, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-12610729, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-12709536, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-12742798, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-12959322, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-12973300, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-1310100, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-14565959, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-15295313, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-15307037, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-15365096, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-15767367, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-16109884, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-16177092, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-17075599, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-17115046, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-18184082, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-1906500, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-2644368, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-3313729, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-7381211, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-7644477, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-7797936, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-8277180, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-8877420, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-9067091, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-9363937, http://linkedlifedata.com/resource/pubmed/commentcorrection/18524817-9769325
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1098-5514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7790-8
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Human immunodeficiency virus infection alters tumor necrosis factor alpha production via Toll-like receptor-dependent pathways in alveolar macrophages and U1 cells.
pubmed:affiliation
Center for HIV/AIDS Care and Research, Boston University School of Medicine, Boston, MA 02118-2393, USA. mnicol@bu.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural