ABSTRACT
The present study investigated the effects of vitamin D deficiency on T cell subsets in patients with spinal tuberculosis. In addition, the influence of vitamin D deficiency was investigated on the expression of cytokines IL-1ß, IL-6 and TNF-α in intervertebral disc lesions of patients. One hundred and seventeen patients with spinal tuberculosis who received operative treatment in the Department of Orthopedics in Wuhan City Third Hospital from March 2012 to March 2015 were collected. The patients were divided depending upon vitamin D content into the control group (64 cases, vitamin D content <25 nmol/l) and experimental group (53 cases, vitamin D content >50 nmol/l). Immunofluorescence method was applied to determine the content of T cell subsets in both groups of patients. Intervertebral disc lesion tissues of two groups of patients were obtained during surgery then treated with HE staining and immunohistochemical staining. The values of average optical density obtained under light microscope were observed as the expression quantities of IL-1ß, IL-6 and TNF-α, to explore the relationship between vitamin D and the expression of cytokines. When vitamin D is lacking, the expression of T lymphocyte subsets in patients with spinal tuberculosis significantly decreased. Compared with experimental group, the difference was statistically significant (P<0.05). Further, the expression of cytokines IL-1ß, IL-6 and TNF-α in intervertebral disc lesion tissues of patients with spinal tuberculosis were significantly higher than those of patients with spinal tuberculosis whose vitamin D content was normal (P<0.05). In the control group, vitamin D content was negatively correlated with the expression of IL-1ß, IL-6 and TNF-α. The expression of T lymphocyte subsets in patients with vitamin D deficiency was significantly reduced, and the immune function decreased. The expression of IL-1ß, IL-6 and TNF-α in lesions were significantly higher than those of patients with normal vitamin D content. In addition, the lower the content of vitamin D was, the more active the expression of inflammatory factors were, which was not conducive to the recovery of tuberculosis lesions.
ABSTRACT
UNLABELLED: Using two electrode voltage clamps, we investigated the effects of lidocaine on one type of glutamate transporter, EAAT3, and the role of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) in mediating the lidocaine effects. EAAT3 was expressed in Xenopus oocytes, and membrane currents were recorded after the application of L-glutamate (30 microM). Lidocaine increased glutamate-induced inward currents significantly at 2 concentrations (100 microM and 1 mM), but not at other concentrations. Lidocaine (100 microM) significantly increased the V(max), but not the K(m), of EAAT3 for glutamate compared with control. The action sites of lidocaine on EAAT3 seem to be intracellular, because only intracellularly injected QX314 (permanently charged lidocaine analog) increased the response. The combination of phorbol-12-myrisate-13-acetate, an activator of PKC, and lidocaine did not further increase the responses compared with phorbol-12-myrisate-13-acetate or lidocaine alone, although each of these three groups showed significantly bigger responses than controls. Three PKC inhibitors (staurosporine, calphostin C, and chelerythrine) did not affect the basal EAAT3 activity but abolished lidocaine-enhanced EAAT3 activity. Wortmannin (a specific PI3K inhibitor) inhibited EAAT3 basal activity and lidocaine-enhanced EAAT3 activity. Our results suggest that lidocaine enhances EAAT3 activity at certain concentrations and that PKC and PI3K may mediate these lidocaine effects. IMPLICATIONS: By using the Xenopus oocyte expression system, we investigated the effects of lidocaine on a glutamate transporter (EAAT3). Our findings suggest that lidocaine enhances EAAT3 activity at certain concentrations and that protein kinase C and phosphatidylinositol 3-kinase may mediate these lidocaine effects.
