Okada Kohki, Arai Satoshi, Nakase Hiroshi, Kohno Hisashi, Nakamura Fumihiko, Takeda Mayu, Toda Yoshinobu, Itoh Hiroshi, Adachi Souichi, Ikemoto Masaki
Dept. of Clinical Laboratory Science, Faculty of Health Science, Tenri Health Care University, Nara 632-0018, Japan; Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Immunological Laboratory, Diagnostic Division, Yamasa Shoyu Co. Ltd., Chiba 288-0056, Japan.
Biochem Biophys Res Commun. 2015 Jan 2;456(1):415-20. doi: 10.1016/j.bbrc.2014.11.099. Epub 2014 Dec 6.
The development of ulcerative colitis (UC) is closely associated with abnormally functioning macrophages. Rat S100A8 (r-S100A8) and r-S100A9 (S100 proteins) is abundantly expressed in immune cells of myeloid origin, macrophages; however, it remains unclear why r-S100A9 is dominantly expressed in the macrophages of UC rats (UCR). The purpose of this study was to verify the immunological roles of S100 proteins in UCR. We observed the distribution of S100 protein-positive macrophages in the large colons of UCR using a fluorescent immunological staining method, so that S100 protein-positive macrophages were restricted to the rectal tissues of the UCR, and that the mRNA levels of r-S100A8 and r-S100A9 were up-regulated by stimulation with recombinant rat S100A8 (rr-S100A8) alone and rr-S100A9 alone, respectively. When the changes in the mRNA levels of r-S100A8 and r-S100A9 in macrophages were examined in in vitro study by PCR and real-time PCR, the mRNA levels of anti-inflammatory and inflammatory cytokines increased selectively after stimulation with rr-S100A8 alone and rr-S100A9 alone, respectively. These results suggest that autocrine signal transduction pathways involving S100 proteins regulate the immunological functions of macrophages to maintain homeostasis in the gastrointestinal tract. This may be depended on expression balance of S100 proteins in macrophages. It is strongly suggested that in UCR the immune functions of macrophages are regulated in a complex manner by r-S100A8 and/or r-S100A9 through undefined autocrine pathways on the cells.
溃疡性结肠炎（UC）的发生与巨噬细胞功能异常密切相关。大鼠S100A8（r-S100A8）和r-S100A9（S100蛋白）在髓系来源的免疫细胞即巨噬细胞中大量表达；然而，尚不清楚为何r-S100A9在UC大鼠（UCR）的巨噬细胞中占主导表达。本研究的目的是验证S100蛋白在UCR中的免疫作用。我们采用荧光免疫染色法观察UCR大鼠结肠中S100蛋白阳性巨噬细胞的分布，结果显示S100蛋白阳性巨噬细胞局限于UCR大鼠的直肠组织，并且单独用重组大鼠S100A8（rr-S100A8）和单独用rr-S100A9刺激分别上调了r-S100A8和r-S100A9的mRNA水平。在体外研究中通过PCR和实时PCR检测巨噬细胞中r-S100A8和r-S100A9的mRNA水平变化时，单独用rr-S100A8和单独用rr-S100A9刺激后，抗炎和炎性细胞因子的mRNA水平分别选择性增加。这些结果表明，涉及S100蛋白的自分泌信号转导途径调节巨噬细胞的免疫功能以维持胃肠道的稳态。这可能取决于巨噬细胞中S100蛋白的表达平衡。强烈提示，在UCR中，巨噬细胞的免疫功能通过r-S100A8和/或r-S100A9通过细胞上未明确的自分泌途径以复杂方式调节。
