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Trigeminal neuropathic pain (TNP) is a significant health problem but the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. Here, we show that TLR8 was persistently increased in the trigeminal ganglion (TG) neurons in model of TNP induced by partial infraorbital nerve ligation (pIONL). In addition, deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38-MAPK, and decreased the expression of pro-inflammatory cytokines in the TG. Furthermore, intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity. VTX-2337 also increased the intracellular Ca
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Objective@#To determine the impact and mechanism of HIV derived microRNA99 (miRNA99) on macrophages pyroptosis.@*Methods@#THP-1 cells were stimulated by phorbol ester (PMA) and then were cultured and differentiated into sidewall attached macrophages; the morphology and phenotype of CD11b were measured by microscopy and flow cytometry. TLR8 RNAi plasmid was transfected to macrophages and were detected by confocal fluorescence microscopy. The levels of IL-18 and IL-1β released by macrophages were measured by ELISA. Western blot(WB) was employed to examine TLR8 and cleaved caspase-1 protein expression in macrophages.@*Results@#THP-1 cells that were challenged with PMA (100 ng/ml) for 24 h became smooth and adherent. In addition, the expression of CD11b in macrophages was up to 99%. TLR8 protein expression in macrophages transfected with TLR8 plasmids was significantly lower than that in macrophages transfected with control plasmids. Levels of IL-18 and IL-1β secreted by macrophages were elevated in LPS+ ATP group, miRNA99 group and control plasmid group, but not in control group and TLR8 RNAi plasmid group. Cleaved caspase-1 protein from macrophages of miRNA99 experimental group/ LPS+ ATP group and control plasmid group was significantly higher than that of control group and TLR8 RNAi plasmid group.@*Conclusions@#The present study demonstrates that HIV-derived miRNA99 could induce pyroptosis of macrophages via TLR8-dependent pathway.
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Objective To examine the expression of TLR7/8 in monocytes purified from HIV-1 infected individuals and to study its association with disease progression. Methods Sixty-three HIV-1 infected individuals and 18 normal controls were enrolled. Monocytes were purified by MACS system and RNA of them was extracted by RNA mini kit of QIAGEN company. TLR7/8 expression was tested by real-time RT-PCR with ABI7500. Results It was found that the expression of TLR7 was strongly correlated with absolute CD4 count (r =0.614, P＜0.01) , so was TLR8 (r =0.419, P＜0.01). The expression of TLR7 in slow progressor (SP) group was higher than that in HIV-1 infected patients group, AIDS patients group and normal group (P ＜ 0. 05 ) . HIV group and normal group were strongly higher than AIDS group (P ＜ 0. 05). It was no significant differentiation of expression of TLR7 between HIV infection group and normal control group. The expression of TLR8 in SP group and normal group were significantly higher than that in AIDS group (P ＜ 0. 05). The expression of TLR8 was no singnificantly difference between SP group and HIV group or normal control group, so was it between HIV group or normal control group and AIDS group. Conclusion The expression of TLR7/8 in monocytes from HIV-1 infected patients significantly correlated with disease progression.