RESUMO
Proinflammatory immune cell subsets constitute the majority in the local microenvironment after spinal cord injury (SCI), leading to secondary pathological injury. Previous studies have demonstrated that inflammasomes act as an important part of the inflammatory process after SCI. Probenecid, an inhibitor of the Pannexin-1 channel, can inhibit the activation of inflammasomes. This article focuses on the effects of probenecid on the local immune microenvironment, histopathology, and behavior of SCI. Our data show that probenecid inhibited the expression and activation of nucleotide-binding oligomerization domain receptor pyrindomain-containing 1 (NLRP1), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1, interleukin-1ß (IL-1ß), and caspase-3 proteins associated with inflammasomes, thereby suppressing the proportion of M1 cells. And consequently, probenecid reduced the lesion area and demyelination in SCI. Moreover, the drug increased the survival of motor neurons, which resulted in tissue repair and improved locomotor function in the injured SC. Altogether, existing studies indicated that probenecid can alleviate inflammation by blocking Pannexin-1 channels to inhibit the expression of caspase-1 and IL-1ß, which in turn restores the balance of immune cell subsets and exerts neuroprotective effects in rats with SCI.
RESUMO
OBJECTIVE: To investigate the effects of low molecular peptide of Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg-10k) on the production of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in peripheral blood T cells and test the feasibility of differential diagnosis between pulmonary tuberculosis (PTB) and latent tuberculosis infection (LTBI) by assessing the number of Mtb-HAg-10k-stimulated IFN-γ-producing T cells. METHODS: Peripheral blood mononuclear cells (PBMCs) were separated from the peripheral blood of 10 healthy adults, 6 individuals with LTBI and 13 patients with PTB. The PBMCs were cultured in the presence of Mtb-HAg-10k obtained by ultrafiltration centrifugation, with Mtb-HAg and phytohaemagglutinin (PHA) as the controls. The proportions of TNF-α- and IFN-γ-producing cells in the T cell subsets were detected by flow cytometry (FCM), and the number of IFN-γ-producing cells from patients with PTB and LTBI was detected with ELISPOT. RESULTS: Flow cytometry showed that Mtb-HAg-10k exposure resulted in a significantly higher proportion of TNF-α-producing γδT cells than that of IFN-γ-producing γδT cells in the PBMCs (P<0.01). Compared with the PBMCs exposed to PHA, the PBMCs exposed to Mtb-HAg-10k exhibited a significantly greater proportion of γδT cells that produced both TNF-α and IFN-γ (P<0.01) but a significantly lower proportion of αßT cells producing both TNF-α and IFN-γ (P<0.01). Mtb-HAg-10k exposure of the PBMCs caused a significant reduction in the number of IFN-γ-producing cells as compared with Mtb-HAg and PHA treatments (P<0.01), and this reduction was more obvious in PBMCs from patients with PTB than in those from individuals with LTBI (P<0.01). CONCLUSION: Mtb-HAg-10k can markedly induce γδT cells in the PBMCs to produce TNF-α and IFN-γ, and detection of the number of IFN-γ-producing cells in the PBMCs following Mtb-HAg-10k stimulation helps in the differential diagnosis between pulmonary tuberculosis and latent tuberculosis infection.