Hernández-Chirlaque Cristina, Aranda Carlos J, Ocón Borja, Polo Javier, Martínez-Augustin Olga, Sánchez de Medina Fermín
Department of Biochemistry and Molecular Biology II, School of Pharmacy, CIBERehd, Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, 18071 Granada, Spain.
Department of Pharmacology, CIBERehd, School of Pharmacy, Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, 18071 Granada, Spain.
Animals (Basel). 2021 Mar 13;11(3):807. doi: 10.3390/ani11030807.
Serum protein concentrates have been shown to exert in vivo anti-inflammatory effects. Specific effects on different cell types and their mechanism of action remain unraveled. We aimed to characterize the immunomodulatory effect of two porcine plasma protein concentrates, spray dried serum (SDS) and an immunoglobulin concentrate (IC), currently used as animal nutritional supplements with established in vivo immunomodulatory properties. Cytokine production by the intestinal epithelial cell line IEC18 and by primary cultures of rat splenocytes was studied. The molecular pathways involved were explored with specific inhibitors and gene knockdown. Our results indicate that both products induced GROα and MCP-1 production in IEC18 cells by a MyD88/NF-κB-dependent mechanism. Inhibition of TNF production was observed in rat primary splenocyte cultures. The immunoglobulin concentrate induced IL-10 expression in primary splenocytes and lymphocytes. The effect on TNF was independent of IL-10 production or the stimulation of NF-kB, MAPKs, AKT, or RAGE. In conclusion, SDS and IC directly regulate intestinal and systemic immune response in murine intestinal epithelial cells and in T lymphocytes and monocytes.
血清蛋白浓缩物已被证明在体内具有抗炎作用。其对不同细胞类型的具体作用及其作用机制仍未明确。我们旨在表征两种猪血浆蛋白浓缩物，即喷雾干燥血清（SDS）和免疫球蛋白浓缩物（IC）的免疫调节作用，这两种浓缩物目前用作具有已确定的体内免疫调节特性的动物营养补充剂。研究了肠上皮细胞系IEC18和大鼠脾细胞原代培养物中细胞因子的产生情况。使用特异性抑制剂和基因敲低技术探索了其中涉及的分子途径。我们的结果表明，两种产品均通过MyD88/NF-κB依赖性机制诱导IEC18细胞产生GROα和MCP-1。在大鼠原代脾细胞培养物中观察到TNF产生受到抑制。免疫球蛋白浓缩物诱导原代脾细胞和淋巴细胞中IL-10的表达。对TNF的作用独立于IL-10的产生或对NF-κB、MAPKs、AKT或RAGE的刺激。总之，SDS和IC直接调节小鼠肠上皮细胞以及T淋巴细胞和单核细胞中的肠道和全身免疫反应。
