CD40-CD40L interactions induce chemokine expression by human microglia

Implications for human immunodeficiency virus encephalitis and multiple sclerosis

Teresa G. D'Aversa, Karen M. Weidenheim, Joan W. Berman

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

CD40 is a protein on microglia that is up-regulated with interferon (IFN)-γ and is engaged by CD40L, found on CD4+ T cells, B cells, and monocytes. These interactions may be important in central nervous system inflammatory diseases. Microglia have been shown to be a source of chemokines, whose expression plays a key role in central nervous system pathologies. We examined the expression of CD40 on microglia in human immunodeficiency virus (HIV) encephalitic brain, and the effects of CD40-CD40L interactions on the expression of chemokines by cultured microglia. We found significantly increased numbers of CD40-positive microglia in HIV-infected brain tissue. Treatment of cultured microglia with IFN-γ and CD40L increased expression of several chemokines. IFN-γ- and CD40L-induced MCP-1 protein was mediated by activation of the ERK1/2 MAPK pathway, and Western blot analysis demonstrated phosphorylation of ERK1/2 upon stimulation of microglia. In contrast, IFN-γ- and CD40L-induced IP-10 protein production was mediated by the p38 MAPK pathway. Our data suggest a mechanism whereby CD40L+ cells can induce microglia to secrete chemokines, amplifying inflammatory processes seen in HIV encephalitis and multiple sclerosis, and implicate CD40-CD40L interactions as a target for interventional strategies.

Original languageEnglish (US)
Pages (from-to)559-567
Number of pages9
JournalAmerican Journal of Pathology
Volume160
Issue number2
StatePublished - 2002

Fingerprint

CD40 Ligand
Microglia
Encephalitis
Chemokines
Multiple Sclerosis
HIV
Interferons
Proteins
MAP Kinase Signaling System
Central Nervous System Diseases
Brain
p38 Mitogen-Activated Protein Kinases
Monocytes
B-Lymphocytes
Central Nervous System
Western Blotting
Phosphorylation
Pathology
T-Lymphocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{ce2518f6f841477f8b89afe74308e497,
title = "CD40-CD40L interactions induce chemokine expression by human microglia: Implications for human immunodeficiency virus encephalitis and multiple sclerosis",
abstract = "CD40 is a protein on microglia that is up-regulated with interferon (IFN)-γ and is engaged by CD40L, found on CD4+ T cells, B cells, and monocytes. These interactions may be important in central nervous system inflammatory diseases. Microglia have been shown to be a source of chemokines, whose expression plays a key role in central nervous system pathologies. We examined the expression of CD40 on microglia in human immunodeficiency virus (HIV) encephalitic brain, and the effects of CD40-CD40L interactions on the expression of chemokines by cultured microglia. We found significantly increased numbers of CD40-positive microglia in HIV-infected brain tissue. Treatment of cultured microglia with IFN-γ and CD40L increased expression of several chemokines. IFN-γ- and CD40L-induced MCP-1 protein was mediated by activation of the ERK1/2 MAPK pathway, and Western blot analysis demonstrated phosphorylation of ERK1/2 upon stimulation of microglia. In contrast, IFN-γ- and CD40L-induced IP-10 protein production was mediated by the p38 MAPK pathway. Our data suggest a mechanism whereby CD40L+ cells can induce microglia to secrete chemokines, amplifying inflammatory processes seen in HIV encephalitis and multiple sclerosis, and implicate CD40-CD40L interactions as a target for interventional strategies.",
author = "D'Aversa, {Teresa G.} and Weidenheim, {Karen M.} and Berman, {Joan W.}",
year = "2002",
language = "English (US)",
volume = "160",
pages = "559--567",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - CD40-CD40L interactions induce chemokine expression by human microglia

T2 - Implications for human immunodeficiency virus encephalitis and multiple sclerosis

AU - D'Aversa, Teresa G.

AU - Weidenheim, Karen M.

AU - Berman, Joan W.

PY - 2002

Y1 - 2002

N2 - CD40 is a protein on microglia that is up-regulated with interferon (IFN)-γ and is engaged by CD40L, found on CD4+ T cells, B cells, and monocytes. These interactions may be important in central nervous system inflammatory diseases. Microglia have been shown to be a source of chemokines, whose expression plays a key role in central nervous system pathologies. We examined the expression of CD40 on microglia in human immunodeficiency virus (HIV) encephalitic brain, and the effects of CD40-CD40L interactions on the expression of chemokines by cultured microglia. We found significantly increased numbers of CD40-positive microglia in HIV-infected brain tissue. Treatment of cultured microglia with IFN-γ and CD40L increased expression of several chemokines. IFN-γ- and CD40L-induced MCP-1 protein was mediated by activation of the ERK1/2 MAPK pathway, and Western blot analysis demonstrated phosphorylation of ERK1/2 upon stimulation of microglia. In contrast, IFN-γ- and CD40L-induced IP-10 protein production was mediated by the p38 MAPK pathway. Our data suggest a mechanism whereby CD40L+ cells can induce microglia to secrete chemokines, amplifying inflammatory processes seen in HIV encephalitis and multiple sclerosis, and implicate CD40-CD40L interactions as a target for interventional strategies.

AB - CD40 is a protein on microglia that is up-regulated with interferon (IFN)-γ and is engaged by CD40L, found on CD4+ T cells, B cells, and monocytes. These interactions may be important in central nervous system inflammatory diseases. Microglia have been shown to be a source of chemokines, whose expression plays a key role in central nervous system pathologies. We examined the expression of CD40 on microglia in human immunodeficiency virus (HIV) encephalitic brain, and the effects of CD40-CD40L interactions on the expression of chemokines by cultured microglia. We found significantly increased numbers of CD40-positive microglia in HIV-infected brain tissue. Treatment of cultured microglia with IFN-γ and CD40L increased expression of several chemokines. IFN-γ- and CD40L-induced MCP-1 protein was mediated by activation of the ERK1/2 MAPK pathway, and Western blot analysis demonstrated phosphorylation of ERK1/2 upon stimulation of microglia. In contrast, IFN-γ- and CD40L-induced IP-10 protein production was mediated by the p38 MAPK pathway. Our data suggest a mechanism whereby CD40L+ cells can induce microglia to secrete chemokines, amplifying inflammatory processes seen in HIV encephalitis and multiple sclerosis, and implicate CD40-CD40L interactions as a target for interventional strategies.

UR - http://www.scopus.com/inward/record.url?scp=0036173719&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036173719&partnerID=8YFLogxK

M3 - Article

VL - 160

SP - 559

EP - 567

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 2

ER -