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[EXPRESS] B14 ameliorates bone cancer pain through down-regulating spinal IL-1β via suppressing neuron JAK2/STAT3 pathway.

著者 Miao X , Ni H , Shen H , Xu LS , Wang Y , Deng H , Yao M
Mol Pain.2019 Oct 15 ; ():1744806919886498.
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Curcumin has several pharmacological properties such as anti-inflammatory, antioxidant, and neuroprotective activities. B14 is a curcumin analogue, and is considered to be a more potent compound with preserved pharmacodynamic activities. Based on previous research studies, janus-activated kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays a remarkable role in inflammation, chronic pain, and even contributes to the pathogenesis of neuropathic pain. Proinflammatory cytokines interleukin (IL)-1β is a downstream factor of JAK2/STAT3 signal transition pathway, which participates in neuron injury and inflammation. We hypothesized that this signal transition pathway played an indispensable role in bone cancer pain (BCP). We herein established a BCP model to monitor the variation of JAK2/STAT3 signal transduction pathway and measured the effect of B14. The results in BCP model showed that: i) the levels of IL-1β were elevated, and the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 were increased; ii) double immunostaining showed that p-JAK2, p-STAT3 and IL-1β were co-localized primarily with neurons, rather than with astrocytes or microglial cells; iii) B14 injection (i.p.) markedly eased BCP; iiii) Western blotting showed that B14 injection lowered p-JAK2, p-STAT3, and IL-1β levels, meanwhile the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 was reduced; iiiii) immunofluorescence results also confirmed decreased levels of p-JAK2, p-STAT3, and IL-1β in B14 treatment group. These findings suggested that B14 injection attenuated BCP in rats. This intervention inhibited JAK2/STAT3 cascade activation, down-regulating IL-1β expression in spinal dorsal horn.
PMID: 31615322 [PubMed - as supplied by publisher]
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