Gene interactions and pathways from curated databases and text-mining
J Neurochem 2002, PMID: 12421347

Expression of interleukin-1 receptors and their role in interleukin-1 actions in murine microglial cells.

Pinteaux, Emmanuel; Parker, Lisa C; Rothwell, Nancy J; Luheshi, Giamal N

Interleukin (IL)-1 is an important mediator of acute brain injury and inflammation, and has been implicated in chronic neurodegeneration. The main source of IL-1 in the CNS is microglial cells, which have also been suggested as targets for its action. However, no data exist demonstrating expression of IL-1 receptors [IL-1 type-I receptor (IL-1RI), IL-1 type-II receptor (IL-1RII) and IL-1 receptor accessory protein (IL-1RAcP)] on microglia. In the present study we investigated whether microglia express IL-1 receptors and whether they present target or modulatory properties for IL-1 actions. RT-PCR analysis demonstrated lower expression of IL-1RI and higher expression of IL-1RII mRNAs in mouse microglial cultures compared with mixed glial or pure astrocyte cultures. Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 (PGE2), and activated nuclear factor kappaB (NF-kappaB) and the mitogen-activated protein kinases (MAPKs) p38, and extracellular signal-regulated protein kinase (ERK1/2), but not c-Jun N-terminal kinase (JNK) in microglial cultures. In comparison, IL-1beta induced the release of PGE2, IL-6 and activated NF-kappaB, p38, JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures. IL-1beta also failed to affect LPS-primed microglial cells. Interestingly, a neutralizing antibody to IL-1RII significantly increased the concentration of IL-1beta in the medium of LPS-treated microglia and exacerbated the IL-1beta-induced IL-6 release in mixed glia, providing the first evidence that microglial IL-1RII regulates IL-1beta actions by binding excess levels of this cytokine during brain inflammation.

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Text Mining Data

p38 → IL-1beta: " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta , IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38 , and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

p38 → IL-6: " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38 , and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

p38 → lipopolysaccharide (LPS): " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38 , and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-1RII → IL-1beta: " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta , IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-1RI → IL-6: " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI , IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-1RI → lipopolysaccharide (LPS): " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI , IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-1beta → IL-1RAcP: " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta , IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-1beta → lipopolysaccharide (LPS): " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta , IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-1beta → c-Jun N-terminal kinase (JNK): " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta , IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-1beta → nuclear factor kappaB (NF-kappaB): " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta , IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-1RAcP → IL-6: " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-1RAcP → lipopolysaccharide (LPS): " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-6 → lipopolysaccharide (LPS): " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-6 → c-Jun N-terminal kinase (JNK): " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

IL-6 → nuclear factor kappaB (NF-kappaB): " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

c-Jun N-terminal kinase (JNK) → lipopolysaccharide (LPS): " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

nuclear factor kappaB (NF-kappaB) → lipopolysaccharide (LPS): " Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 ( PGE2 ), and activated nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases ( MAPKs ) p38, and extracellular signal regulated protein kinase ( ERK1/2 ), but not c-Jun N-terminal kinase (JNK) in microglial cultures "

p38 → IL-1beta: " In comparison, IL-1beta induced the release of PGE2, IL-6 and activated NF-kappaB, p38 , JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures "

p38 → IL-1beta: " In comparison, IL-1beta induced the release of PGE2, IL-6 and activated NF-kappaB, p38 , JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures "

ERK1/2 → IL-1beta: " In comparison, IL-1beta induced the release of PGE2, IL-6 and activated NF-kappaB, p38, JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures "

ERK1/2 → IL-1beta: " In comparison, IL-1beta induced the release of PGE2, IL-6 and activated NF-kappaB, p38, JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures "

IL-1beta → IL-6: " In comparison, IL-1beta induced the release of PGE2, IL-6 and activated NF-kappaB, p38, JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures "

IL-1beta → NF-kappaB: " In comparison, IL-1beta induced the release of PGE2, IL-6 and activated NF-kappaB , p38, JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures "

IL-1beta → IL-6: " In comparison, IL-1beta induced the release of PGE2, IL-6 and activated NF-kappaB, p38, JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures "

IL-1beta → NF-kappaB: " In comparison, IL-1beta induced the release of PGE2, IL-6 and activated NF-kappaB , p38, JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures "

IL-6 → IL-1beta: " Interestingly, a neutralizing antibody to IL-1RII significantly increased the concentration of IL-1beta in the medium of LPS treated microglia and exacerbated the IL-1beta induced IL-6 release in mixed glia, providing the first evidence that microglial IL-1RII regulates IL-1beta actions by binding excess levels of this cytokine during brain inflammation "

Manually curated Databases

No curated data.