Up-regulation of FPR2, a chemotactic receptor for amyloid beta 1-42 (A beta 42), in murine microglial cells by TNF alpha.
Human FPRL1 and its mouse homologue FPR2 are functional receptors for several exogenous and host-derived chemotactic peptides, including amyloid beta(42) (A beta(42)), a critical pathogenic factor in Alzheimer's disease. We investigated the effect of TNF alpha on the expression and function of FPR2 in mouse microglial cells, a crucial inflammatory cell type in the CNS. Primary murine microglia and a cell line N9 in resting state expressed low levels of FPR2 gene and lacked the response to chemotactic agonists for this receptor. Incubation with TNF alpha, however, increased microglial expression of FPR2 gene, in association with potent chemotactic responses to FPR2-specific agonists including A beta(42). The effect of TNF alpha was dependent on the p55 TNF alpha receptor and activation of MAP kinase p38. TNF alpha concomitantly down-regulated microglial response to the chemokine SDF-1 alpha. Thus, by selectively up-regulating FPR2 in microglia, TNF alpha has the capacity to amplify host response in inflammatory diseases in the CNS.
Cui
Y H
YH
Laboratory of Molecular immunoregulation, Center for Cancer Research, SAIC Frederick, National Cancer Institute at Frederick, National Institutes of Health, MD 27110, USA.
Le
Y
Y
Zhang
X
X
Gong
W
W
Abe
K
K
Sun
R
R
Van Damme
J
J
Proost
P
P
Wang
J M
JM
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D016229:Amyloid beta-Peptides; C105101:FPR2 protein, human; D010446:Peptide Fragments; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42)