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Objectives: To investigate the effects of the oestradiol (ES) pulsed bone marrow-derived mesenchymal stem cells (BM-MSC) to treat adjuvant-induced arthritis in Wistar rats. Materials and Methods: BM-MSCs were pulsed with ES (0, 10,100, and 1000 nM) for 24 hr. RA was induced by collagen and Freund's Complete Adjuvant into the base of the tail of Wistar rats. Results: The least effective concentration of ES that can promote potent anti-inflammatory properties in the MSC population is 100 nM. At this concentration, ES increases the inhibition of the polyclonal T lymphocyte proliferation, production of IDO, IL-10, Nitric oxide, and TGF-ß, and expression of CXCR4 and CCR2 mRNA in the MSC population. Accordingly, the RA rats were treated with 2×106 MSCs or ES-pulsed MSCs (100 nM) on day 10 when all animals had developed signs of RA. ES-pulsed BM-MSCs reduced the severity of RA more profoundly than treatment with BM-MScs alone. The ability of ES-pulsed BM-MSCs to reduce symptoms and RA markers like CRP, RF, and nitric oxide was comparable to that of prednisolone. Prednisolone was more successful in reducing inflammatory cytokines than treatment with ES-pulsed BM-MSCs. ES-pulsed BM-MSCs were more successful in increasing anti-inflammatory cytokines than treatment with Prednisolone. The ability of ES-pulsed BM-MSCs to decrease the level of nitric oxide was comparable to that of prednisolone. Conclusion: ES-pulsed BM-MSCs may be a helpful strategy in RA control.
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OBJECTIVE: Thymol, a natural aromatic monoterpene phenol derived from thymus, possesses anti-inflammatory benefits. Here, we evaluated the potential of thymol therapy in improving an animal model of ulcerative colitis. MATERIALS AND METHODS: Luminal instillation of acetic acid was used to induce colitis in male Wistar rats. Treatment groups daily received prednisolone (2 mg/kg, orally) or thymol (100 mg/kg, orally) for 10 consecutive days. Then, the rats were euthanized and tissue specimens were collected for evaluation of cyclooxygenase-2 (COX-2) expression by immunohistochemistry. Furthermore, the levels of total protein, nitric oxide, myeloperoxidase, malondialdehyde, IL-1, IL-6, and TNF-α were monitored in colonic homogenates. Eventually, the relative mRNA expression of IκBα and NF-κBp65 was investigated using reverse-transcriptase PCR (RT-PCR) in colonic homogenates. RESULTS: Both medications could reduce the mortality rate and the clinical scores of ulcerative colitis. The COX-2 expression was significantly reduced in the colons of thymol-treated animals compared to the prednisolone group. Also, the myeloperoxidase activity, nitric oxide level and malondialdehyde intensity were decreased in the colons of thymol-treated animals to a greater extent compared to the prednisolone group. Moreover, the total protein content of guts showed significant increases in the guts of thymol-treated animals in comparison to the prednisolone group. Nonetheless, thymol significantly reduced the levels of IL-6, and IL-1 compared to prednisolone. Both medications caused a significant decrease in the mRNA level of NF-κBp65, though the mRNA level of IκBα did not show significant changes between the groups. CONCLUSION: Thymol may be a promising agent to ameliorate ulcerative colitis.
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BACKGROUND: This study was conducted to determine the potential of the monocytes educated with rat bone marrow mesenchymal stem cell-derived conditioned medium (MCM) in ameliorating animal model of asthma. METHODS: Chronic asthma was induced in the BALB/c mice using ovalbumin (OVA) sensitization. The monocytes were isolated from blood of mice and supplemented with 50% MCM or negative control media. After 24 h, the cells were designated as "non-educated or educated". Fourteen weeks after the onset of the study, animals were treated with educated or non-educated monocytes twice with a 1-week interval. RESULTS: The educated monocytes showed a reduction in the potential production of the respiratory burst and nitric oxide and the secretion of IL-12 and IL-4 compared to non-educated monocytes. Conversely, these monocytes exhibited a significant increase in the production of IL-10 and TGF-?. Also, the levels of CD68+/CD206+ cells significantly increased in the population of educated monocytes. More importantly, the severity of histopathological lesions, NF-?B p65 mRNA level in lung tissues, total serum IgE and the total cell count, as well as the eosinophil count in the bronchoalveolar lavage fluid, were significantly decreased in OVA-inhaled mice treated with educated monocytes compared to OVA-sensitized group receiving non-educated monocytes. With no advantage in up-regulation of Foxp3 Treg cells, the treatment with educated monocytes reduced the secretion of IL-5 and IL-13 by splenocytes of asthma mice more than splenocytes of the asthma mice treated with non-educated monocytes. CONCLUSION: The educated monocytes with MCM may be as a promising strategy for cell-based therapies of asthma.
