Elahi Asif, Singh M P, Ali Shakir, Khan Farah
Department of Biochemistry, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India.
Advance Instrumentation Research Facility, Jawaharlal Nehru University, JNU Ring Road, New Delhi, 110067, India.
Int Immunopharmacol. 2014 Jul;21(1):82-93. doi: 10.1016/j.intimp.2014.04.013. Epub 2014 May 2.
The present study evaluated mineral compound, pearl in ashed form [PAF], for its potential as oral immunomodulator. ICP-MS, atomic absorption spectroscopy, CHNS analysis and XRD analysis were used for characterization of PAF. Surface antigen markers (TLR-2/4 and CD-80/86) were studied by flow cytometry. At dose concentration of 25, 50, 100 and 500 μg/kg body wt., administrated orally for 10 days, TLR-2 expression on murine peritoneal macrophage increased while TLR-4 expression was reduced as compared to control. There was an increase in OVA and mitogen (Con-A) specific lymphocyte proliferation in OVA immunized mice. Also, level of both Th1 (IL-2/IFN-γ) and Th2 (IL-4/IL-10) cytokines, and level and titer of total IgG, IgG1, IgG2a and IgG2b of OVA immunized mice significantly increased. The level of Inflammatory cytokines (IL-1β and TNF-α) did not increase significantly. Enhancement in T and B cell immune responses may be possibly due to significantly enhanced expression of CD-80 and CD-86 co-stimulatory signals as observed using flow cytometry. Also, enhanced phagocytic activity and DTH response exhibit stimulatory effect of PAF on innate and cell mediated immune response. Histopathological analysis of liver, kidney and spleen and analysis of other toxicity parameters, such as effect on body weight, lymphoid organ weight and cellularity, revealed PAF to exhibit no toxic effects. PAF seems to be a promising balanced Th1 and Th2 directing immunomodulator, possibly activating TLR2 through TIR domain-containing adaptor inducing interferon β (TRIF)-dependent pathway that leads to T-cell activation and promotes effective immune responses and may find useful application clinically.
本研究评估了矿物化合物——灰化形式的珍珠[PAF]作为口服免疫调节剂的潜力。采用电感耦合等离子体质谱法(ICP-MS)、原子吸收光谱法、CHNS分析和X射线衍射分析(XRD分析)对PAF进行表征。通过流式细胞术研究表面抗原标志物(TLR-2/4和CD-80/86)。以25、50、100和500μg/kg体重的剂量浓度口服给药10天,与对照组相比,小鼠腹腔巨噬细胞上TLR-2的表达增加,而TLR-4的表达降低。在卵清蛋白(OVA)免疫的小鼠中,OVA和丝裂原(刀豆蛋白A)特异性淋巴细胞增殖增加。此外,OVA免疫小鼠的Th1(白细胞介素-2/干扰素-γ)和Th2(白细胞介素-4/白细胞介素-10)细胞因子水平以及总IgG、IgG1、IgG2a和IgG2b的水平和滴度均显著增加。炎性细胞因子(白细胞介素-1β和肿瘤坏死因子-α)水平未显著增加。T细胞和B细胞免疫反应的增强可能是由于使用流式细胞术观察到的CD-80和CD-86共刺激信号的显著增强表达。此外,增强的吞噬活性和迟发型超敏反应(DTH)反应显示PAF对固有免疫和细胞介导的免疫反应具有刺激作用。肝脏、肾脏和脾脏的组织病理学分析以及其他毒性参数分析,如对体重、淋巴器官重量和细胞数量的影响,显示PAF无毒性作用。PAF似乎是一种有前景的平衡Th1和Th2的免疫调节剂,可能通过含TIR结构域的接头诱导干扰素β(TRIF)依赖性途径激活TLR2,该途径导致T细胞活化并促进有效的免疫反应,可能在临床上有有用的应用。