Routray Indusmita, Ali Shakir
Department of Biochemistry, Faculty of Science, Jamia Hamdard Deemed University, Hamdard Nagar, New Delhi, 110062, India.
PLoS One. 2016 Mar 2;11(3):e0150607. doi: 10.1371/journal.pone.0150607. eCollection 2016.
Chemical mediators of inflammation (CMI) are important in host defense against infection. The reduced capacity of host to induce the secretion of these mediators following infection is one of the factors in host susceptibility to infection. Boron, which has been suggested for its role in infection, is reported in this study to increase lymphocyte proliferation and the secretion of CMI by the lipopolysaccharide (LPS)-stimulated peritoneal macrophages in BALB/c mice. Boron was administered to mice orally as borax at different doses for 10 consecutive days, followed by the stimulation of animals with ovalbumin and isolation of splenocytes for proliferation assay. The lymphocyte subsets were determined by flow cytometry in spleen cell suspension. The mediators of inflammation, TNF-α, IL-6, IL-1β and nitric oxide (NO), were measured in culture supernatant of LPS-primed macrophages isolated from borax treated mice. TNF and ILs were measured by ELISA. NO was determined by Griess test. The expression of inducible nitric oxide synthase (iNOS) in macrophages was studied by confocal microscopy. Results showed a significant increase in T and B cell populations, as indicated by an increase in CD4 and CD19, but not CD8, cells. Boron further stimulated the secretion of TNF-α, IL-6, IL-1β, NO and the expression of iNOS by the LPS-primed macrophages. The effect was dose dependent and most significant at a dose level of 4.6 mg/kg b. wt. Taken together, the study concludes that boron at physiological concentration induces lymphocyte proliferation and increases the synthesis and secretion of pro-inflammatory mediators by the LPS-primed macrophages, more specifically the M1 macrophages, possibly acting through Toll-like receptor. The study implicates boron as a regulator of the immune and inflammatory reactions and macrophage polarization, thus playing an important role in augmenting host defense against infection, with possible role in cancer and other diseases.
炎症化学介质（CMI）在宿主抗感染防御中起着重要作用。宿主在感染后诱导这些介质分泌的能力降低是宿主易感染的因素之一。硼因其在感染中的作用而受到关注，本研究报道硼可增加BALB/c小鼠中脂多糖（LPS）刺激的腹腔巨噬细胞的淋巴细胞增殖和CMI分泌。将硼以硼砂的形式不同剂量连续10天口服给予小鼠，随后用卵清蛋白刺激动物并分离脾细胞进行增殖测定。通过流式细胞术测定脾细胞悬液中的淋巴细胞亚群。在从硼砂处理的小鼠中分离的LPS预处理巨噬细胞的培养上清液中测量炎症介质TNF-α、IL-6、IL-1β和一氧化氮（NO）。通过ELISA测量TNF和ILs。通过Griess试验测定NO。通过共聚焦显微镜研究巨噬细胞中诱导型一氧化氮合酶（iNOS）的表达。结果显示T细胞和B细胞群体显著增加，表现为CD4和CD19细胞增加，但CD8细胞未增加。硼进一步刺激LPS预处理巨噬细胞分泌TNF-α、IL-6、IL-1β、NO以及iNOS的表达。该作用呈剂量依赖性，在剂量水平为4.6mg/kg体重时最为显著。综上所述，该研究得出结论，生理浓度的硼可诱导淋巴细胞增殖，并增加LPS预处理巨噬细胞，更具体地说是M1巨噬细胞的促炎介质合成和分泌，可能通过Toll样受体起作用。该研究表明硼是免疫和炎症反应以及巨噬细胞极化的调节剂，因此在增强宿主抗感染防御中起重要作用，可能在癌症和其他疾病中也发挥作用。
