Attenuated TLR4/MAPK signaling in monocytes from patients with CRMO results in impaired IL-10 expression
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
Abstract
Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder of unknown origin. We previously demonstrated that monocytes from CRMO patients fail to express the immune-modulatory cytokine interleukin‐10 (IL‐10) in a chromatin dependent manner. Here, we demonstrate that attenuated extracellular-signal regulated kinase (ERK)1 and 2 signaling in response to TLR4 activation results in failure to induce IL-10 expression in monocytes from CRMO patients. Attenuated ERK1/2 activation results in 1) reduced levels of Sp-1, a transcription factor that induces IL-10 expression in monocytes, and 2) impaired H3S10 phosphorylation of the IL10 promoter, an activating epigenetic mark. The pro-inflammatory cytokines tumor necrosis factor (TNF)α and IL-6 are not negatively affected, resulting in an imbalance towards pro-inflammatory cytokines. Thus, impaired ERK1/2 signaling with subsequently reduced Sp-1 expression and H3S10 phosphorylation of the IL10 promoter may centrally contribute to the pathophysiology of CRMO
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 69-76 |
Seitenumfang | 8 |
Fachzeitschrift | Clinical Immunology |
Jahrgang | 145 |
Ausgabenummer | 1 |
Publikationsstatus | Veröffentlicht - Okt. 2012 |
Peer-Review-Status | Ja |
Externe IDs
Scopus | 84865459912 |
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