Effects of FR‐91 on Immune Cells from Healthy Individuals and from Patients with Non‐Hodgkin Lymphoma

Lombardi, Valter; Martínez, E.; Chacón, R.; Etcheverría, Ignacio; Cacabelos, Ramón

doi:10.1155/2009/187015

Cited by 3 publications

(3 citation statements)

References 52 publications

(36 reference statements)

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“…It has also been shown that the upregulation of Cx43 expression can promote the activation of CD4 + T lymphocytes ( 10 , 16 , 38 ). Given that arterial hypertension activates T lymphocytes ( 1 ), ConA is used as a T cell activator that induces various cytokine secretions ( 39 , 40 ). In addition, to confirm the involvement of GJs in lymphocyte proliferation after activation, lymphocytes were treated with a Cx extracellular loop mimetic peptide (Gap27), which can restrictintercellular communication across GJs and reduce or block Cx hemichannel function in CD4 + T cells and other cell systems (i.e., non-diabetic cells) ( 16 , 41 ).…”

Section: Discussionmentioning

confidence: 99%

Connexin 43 in splenic lymphocytes is involved in the regulation of CD4+CD25+ T lymphocyte proliferation and cytokine production in hypertensive inflammation

Zhang

et al. 2017

Int J Mol Med

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Chronic inflammation promotes the development of hypertension and is associated with increased T cell infiltration and cytokine production in impaired organs. Gap junction protein connexin 43 (Cx43), is ubiquitously expressed in immune cells and plays an important role in T cell proliferation and activation, and cytokine production. However, the correlation between Cx43 in T cells and the hypertensive inflammatory response remains unknown. Thus, in this study, we wished to examine this correlation. First, our results revealed that hypertension caused significant thickening of the vascular wall, inflammatory cell infiltration into part of the renal interstitium and glomerular atrophy, and it increased the tubular damage scores in the kidneys of spontaneously hypertensive rats (SHRs). Moreover, the SHRs exhibited stenosis in the central artery wall of the spleen with increased serum levels of interleukin (IL)-2 and IL-6 compared with normotensive Wistar-Kyoto (WKY) rats. The spleens of the SHRs exhibited a significantly decreased percentage of CD4+CD25+ (Treg) T cells. However, the percentages of CD3+, CD4+ and CD8+ T cell and the levels of CD4+Cx43 and CD8+Cx43 did not differ significantly between the SHRs and WKY rats. In cultured lymphocytes from the SHRs and WKY rats, low percentages of Treg cells and reduced cytokine (IL-2 and IL-6) mRNA expression levels were observed in the lymphocytes obtained from the SHRs and WKY rats treated with the connexin blocker, Gap27, or concanavalin A (ConA) plus Gap27. The effects of ConA and Gap27 differed between the SHRs and WKY rats. On the whole, our findings demonstrate that the splenic Treg cell-mediated suppression in SHRs may be involved in hypertensive inflammatory responses. Cx43 in the gap junctional channel may regulate lymphocyte activation and inflammatory cytokine production.

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Section: Discussionmentioning

confidence: 99%

Connexin 43 in splenic lymphocytes is involved in the regulation of CD4+CD25+ T lymphocyte proliferation and cytokine production in hypertensive inflammation

Zhang

et al. 2017

Int J Mol Med

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“…To detect cytokine inhibition, α-mangostin was combined with ConA to treat PBMCs. ConA is a T-cell activator that subsequently induces various cytokine secretions [11,12]. Ten µg/mL of ConA was not toxic to the cells (> 95% of cell survival) and led to the highest cytokine secretion (data not shown).…”

mentioning

confidence: 93%

Immunomodulatory Activities of α-Mangostin on Peripheral Blood Mononuclear Cells

Kasemwattanaroj

Moongkarndi

Pattanapanyasat

et al. 2013

Natural Product Communications

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Mangosteen (Garcinia mangostana L.) a tropical fruit, has been used in traditional medicine. A frequently used part of mangosteen is the pericarp, containing a high content of xanthones. α-Mangostin, one of the major xanthone derivatives, exhibits a variety of actions, including antimicrobial, antioxidant, cytotoxic and antitumor; however, its function on the immune system is still equivocal. This study aimed to examine the immunomodulatory activities of α-mangostin on lymphocyte lineage and cytokine production in human peripheral blood mononuclear cells (PBMCs). The cytotoxic activity of α-mangostin was measured by MTT assay. The concentration of α-mangostin at 5.55 µg/mL resulted in a 50% survival of PBMCs, which was as potent a cytotoxic activity as that of paclitaxel. After 24 h of PBMCs culture, the percentages of T cells (CD3+), B cells (CD19+) and NK cells (CD3-CD16+CD56+) were not significantly changed by treatment with 1, 2 and 4 µg/mL of α-mangostin compared with untreated-PBMCs; in addition, the percentages of these lymphocytes treated with the combination of α-mangostin (1, 2 and 4 µg/mL) and the mitogen concanavalin A (ConA) was not significantly different from that of ConA-treated PBMCs. For cytokine secretion, α-mangostin (1, 2 and 4 µg/mL) did not significantly induce either proinflammatory cytokines (i.e., TNF-α and IL-1β) or cytokine of adaptive immunity (i.e., IL-2). The combination of α-mangostin (1, 2 and 4 µg/mL) and ConA did not significantly alter the relative difference of TNF-α and IL-1β compared with ConA-treated PBMCs; however, these combinations could significantly decrease the relative difference of IL-2 compared with ConAtreated PBMCs. These data indicated that α-mangostin was able to inhibit IL-2 release without interfering with human immune cells; therefore, further studies are necessary to investigate its effect on IL-2 production.

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“…In the present study, we investigated the effect of FR91, a standardized lysate of microbial cells belonging to the Bacillus genus which has been previously shown to have significant immunomodulatory effects tested on human tumor cell lines [ 12 ], on colonic inflammation induced by 8-week exposure of 2% DSS in the drinking water and, in particular, whether FR91 affects colorectal inflammation. We found that the six-week treatment resulted in a slightly reduction of colorectal lesions at lower dosis (5% FR91) and a moderate-to-complete reduction at higher dosis (10–20% FR91).…”

Section: Discussionmentioning

confidence: 99%

Prevention of Chronic Experimental Colitis Induced by Dextran Sulphate Sodium (DSS) in Mice Treated with FR91

Lombardi

Etcheverría

Carrera

et al. 2012

Journal of Biomedicine and Biotechnology

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One of the main treatments currently used in humans to fight cancer is chemotherapy. A huge number of compounds with antitumor activity are present in nature, and many of their derivatives are produced by microorganisms. However, the search for new drugs still represents a main objective for cancer therapy, due to drug toxicity and resistance to multiple chemotherapeutic drugs. In animal models, a short-time oral administration of dextran sulfate sodium (DSS) induces colitis, which exhibits several clinical and histological features similar to ulcerative colitis (UC). However, the pathogenic factors responsible for DSS-induced colitis and the subsequent colon cancer also remain unclear. We investigated the effect of FR91, a standardized lysate of microbial cells belonging to the Bacillus genus which has been previously shown to have significant immunomodulatory effects, against intestinal inflammation. Colitis was induced in mice during 5 weeks by oral administration 2% (DSS). Morphological changes in the colonic mucosa were evaluated by hematoxylin-eosin staining and immunohistochemistry methods. Adenocarcinoma and cryptal cells of the dysplastic epithelium showed cathenin-β, MLH1, APC, and p53 expression, together with increased production of IFN-γ. In our model, the optimal dose response was the 20% FR91 concentration, where no histological alterations or mild DSS-induced lesions were observed. These results indicate that FR91 may act as a chemopreventive agent against inflammation in mice DSS-induced colitis.

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Effects of FR‐91 on Immune Cells from Healthy Individuals and from Patients with Non‐Hodgkin Lymphoma

Cited by 3 publications

References 52 publications

Connexin 43 in splenic lymphocytes is involved in the regulation of CD4+CD25+ T lymphocyte proliferation and cytokine production in hypertensive inflammation

Connexin 43 in splenic lymphocytes is involved in the regulation of CD4+CD25+ T lymphocyte proliferation and cytokine production in hypertensive inflammation

Immunomodulatory Activities of α-Mangostin on Peripheral Blood Mononuclear Cells

Prevention of Chronic Experimental Colitis Induced by Dextran Sulphate Sodium (DSS) in Mice Treated with FR91

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