ArticleJournal of neuroscience research2008
CD40-CD40 ligand interactions in human microglia induce CXCL8 (interleukin-8) secretion by a mechanism dependent on activation of ERK1/2 and nuclear translocation of nuclear factor-kappaB (NFkappaB) and activator protein-1 (AP-1).
Article in Journal of neuroscience research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
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- CD40 Ligand-CD40 Interaction Is an Intermediary between Inflammation and Angiogenesis in Proliferative Diabetic Retinopathy.International journal of molecular sciences · 2023Article
- Arterial Baroreflex Dysfunction Promotes Neuroinflammation by Activating the Platelet CD40L/Nuclear Factor Kappa B Signaling Pathway in Microglia and Astrocytes.Neurochemical research · 2023Article
- Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells.International journal of molecular sciences · 2022Article
- Molecular docking studies of natural immunomodulators indicate their interactions with the CD40L of CD40/CD40L pathway and CSF1R kinase domain of microglia.Journal of molecular modeling · 2022Article
- Neuroinflammation and EIF2 Signaling Persist despite Antiretroviral Treatment in an hiPSC Tri-culture Model of HIV Infection.Stem cell reports · 2020Article
- Review
- Frontline Science: c-Myc regulates P-selectin glycoprotein ligand-1 expression in monocytes during HIV-1 infection.Journal of leukocyte biology · 2017Article
- Regulatory role of cytosolic phospholipase AJournal of neuroinflammation · 2017Article
- Soluble CD40-ligand (sCD40L, sCD154) plays an immunosuppressive role via regulatory T cell expansion in HIV infection.Clinical and experimental immunology · 2014Article
- Role of peripheral immune response in microglia activation and regulation of brain chemokine and proinflammatory cytokine responses induced during VSV encephalitis.Journal of neuroimmunology · 2014Article
- Chemokine CXCL8 promotes HIV-1 replication in human monocyte-derived macrophages and primary microglia via nuclear factor-κB pathway.PloS one · 2014Article
- Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2013Review
- Coordinated dynamic gene expression changes in the central nucleus of the amygdala during alcohol withdrawal.Alcoholism, clinical and experimental research · 2013Article
- Cytokines and chemokines at the crossroads of neuroinflammation, neurodegeneration, and neuropathic pain.Mediators of inflammation · 2013Review
- Microglia activation by SIV-infected macrophages: alterations in morphology and cytokine secretion.Journal of neurovirology · 2012Article
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- Glia and methylmercury neurotoxicity.Journal of toxicology and environmental health. Part A · 2012Review
- Specific NFkappaB subunit activation and kinetics of cytokine induction in adenoviral keratitis.Molecular vision · 2009Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
CXCL8 is a CXC chemokine that recruits leukocytes to sites of inflammation. Expression of CXCL8 in the CNS has been demonstrated in neuroinflammatory diseases, including human immunodeficiency virus (HIV-1) encephalitis, but the mechanism of secretion of this chemokine is not fully understood. CD40 is a 50-kDa protein on the surface of microglia, and we have previously shown that it is increased in expression in HIV-1-infected brain tissue as well as by interferon-gamma (IFNgamma) in tissue culture. We examined the expression and regulation of CXCL8 in cultured human fetal microglia after ligation of CD40 with soluble trimeric CD40 ligand (sCD40L) as well as the expression of CXCL8 on microglia in HIV encephalitic brain tissue sections. Treatment of cultured microglia with IFNgamma + sCD40L resulted in significant induction of CXCL8. This expression was mediated by activation of the ERK1/2 MAPK pathway, as demonstrated by ELISA and Western blot using a specific inhibitor (U0126). Gel shift analyses demonstrated that NFkappaB and AP-1, but not C/EBPbeta, mediate microglial CXCL8 production. We also found increased colocalization of CXCL8 with CD68/CD40-positive cells in HIV encephalitic brain tissue compared with HIV-infected nonencephalitic and normal tissue. Thus, CD40-CD40L interactions facilitate chemokine expression, leading to the influx of inflammatory cells into the CNS. These events can lead to the pathology that is associated with neuroinflammatory diseases.
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