The immunomodulatory and anti-inflammatory functions of mesenchymal stromal cells (MSCs) have been demonstrated in several autoimmune/inflammatory disease models, but their contribution to the mitigation of contact hypersensitivity (CHS) remains unclear. Here, we report a new immunological approach using human gingiva-derived MSCs (GMSCs) to desensitize and suppress CHS and the underlying mechanisms. Our results showed that systemic infusion of GMSCs before the sensitization and challenge phase dramatically suppress CHS, manifested as a decreased infiltration of dendritic cells (DCs), CD8 1 T cells, T H -17 and mast cells (MCs), a suppression of a variety of inflammatory cytokines, and a reciprocal increased infiltration of regulatory T cells and expression of IL-10 at the regional lymph nodes and the allergic contact areas. The GMSC-mediated immunosuppressive effects and mitigation of CHS were significantly abrogated on pretreatment with indomethacin, an inhibitor of cyclooxygenases. Under coculture condition of direct cell-cell contact or via transwell system, GMSCs were capable of direct suppression of differentiation of DCs and phorbol 12-myristate 13-acetate-stimulated activation of MCs, whereas the inhibitory effects were attenuated by indomethacin. Mechanistically, GMSC-induced blockage of de novo synthesis of proinflammatory cytokines by MCs is mediated partly by the tumor necrosis factor-alpha/prostaglandin E 2 (PGE 2 ) feedback axis. These results demonstrate that GMSCs are capable of desensitizing allergic contact dermatitis via PGE 2 -dependent mechanisms.
AIM:To compare the expression patterns of cholecystokinin-B (CCK-B)/gastrin receptor genes in matched human gastric carcinoma and adjacent non-neoplastic mucosa of patients with gastric cancer, inflammatory gastric mucosa from patients with gastritis, normal stomachs from 2 autopsied patients and a gastric carcinoma cell line (SGC-7901), and to explore their relationship with progression to malignancy of human gastric carcinomas. METHODS:RT-PCR and sequencing were employed to detect the mRNA expression levels of CCK-B receptor and gastrin gene in specimens from 30 patients with gastric carcinoma and healthy bordering non-cancerous mucosa, 10 gastritis patients and normal stomachs from 2 autopsied patients as well as SGC-7901. The results were semi-quantified by normalizing it to the mRNA level of β-actin gene using Lab Image software. The sequences were analyzed by BLAST program. RESULTS:CCK-B receptor transcripts were detected in all of human gastric tissues in this study, including normal, inflammatory and malignant tissues and SGC-7901. However, the expression levels of CCK-B receptor in normal gastric tissues were higher than those in other groups (P<0.05), and its expressions did not correlate with the differentiation and metastasis of gastric cancer (P>0.05). On the other hand, gastrin mRNA was detected in SGC-7901 and in specimens obtained from gastric cancer patients (22/30) but not in other gastric tissues, and its expression was highly correlated with the metastases of gastric cancer (P<0.05).
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