Immunomodulatory Effects of Human Cryopreserved Viable Amniotic Membrane in a Pro-Inflammatory Environment In Vitro

Junctional epidermolysis bullosa (JEB) is a clinically and genetically heterogeneous skin fragility disorder frequently caused by mutations in genes encoding the epithelial laminin isoform, laminin-332. JEB patients also present mucosal involvement, including painful corneal lesions. Recurrent corneal abrasions may lead to corneal opacities and visual impairment. Current treatments are merely supportive. We report a novel JEB phenotype distinguished by the complete resolution of skin fragility in infancy and persistent ocular involvement with unremitting and painful corneal abrasions. Biallelic LAMB3 mutations c.3052-5C>G and c.3492_3493delCG were identified as the molecular basis for this phenotype, with one mutation being a hypomorphic splice variant that allows residual wild-type laminin-332 production. The reduced laminin-332 level was associated with impaired keratinocyte adhesion. Then, we also investigated the therapeutic power of a human amniotic membrane (AM) eyedrop preparation for corneal lesions. AM were isolated from placenta donors, according to a procedure preserving the AM biological characteristics as a tissue, and confirmed to contain laminin-332. We found that AM eyedrop preparation could restore keratinocyte adhesion in an in vitro assay. Of note, AM eyedrop administration to the patient resulted in long-lasting remission of her ocular manifestations. Our findings suggest that AM eyedrops could represent an effective, non-invasive, simple-to-handle treatment for corneal lesions in patients with JEB and possibly other EB forms.

Download Full-text

The Immunomodulatory Effects of Honey and Associated Flavonoids in Cancer

Nutrients ◽

10.3390/nu13041269 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1269

Author(s):

Razan J. Masad ◽

Shoja M. Haneefa ◽

Yassir A. Mohamed ◽

Ashraf Al-Sbiei ◽

Ghada Bashir ◽

...

Keyword(s):

Immune Responses ◽

Antioxidant Properties ◽

In Vivo Studies ◽

Immunomodulatory Effects ◽

Bioactive Constituents ◽

Cancer Cell Growth ◽

Cancer Types ◽

Immunomodulatory Properties

Honey has exerted a high impact in the field of alternative medicine over many centuries. In addition to its wound healing, anti-microbial and antioxidant properties, several lines of evidence have highlighted the efficiency of honey and associated bioactive constituents as anti-tumor agents against a range of cancer types. Mechanistically, honey was shown to inhibit cancer cell growth through its pro-apoptotic, anti-proliferative and anti-metastatic effects. However, the potential of honey to regulate anti-tumor immune responses is relatively unexplored. A small number of in vitro and in vivo studies have demonstrated the ability of honey to modulate the immune system by inducing immunostimulatory as well as anti-inflammatory effects. In the present review, we summarize the findings from different studies that aimed to investigate the immunomodulatory properties of honey and its flavonoid components in relation to cancer. While these studies provide promising data, additional research is needed to further elucidate the immunomodulatory properties of honey, and to enable its utilization as an adjuvant therapy in cancer.

Download Full-text

Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

Scientific Reports ◽

10.1038/s41598-021-92412-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ana Colado ◽

Esteban Enrique Elías ◽

Valeria Judith Sarapura Martínez ◽

Gregorio Cordini ◽

Pablo Morande ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Chronic Lymphocytic Leukemia ◽

T Cell Activation ◽

Cell Activation ◽

Lymphocytic Leukemia ◽

Immunomodulatory Effects ◽

Immunoglobulin Preparations

AbstractHypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.

Download Full-text

Amniotic membrane induces apoptosis of interferon-γ activated macrophages in vitro

Experimental Eye Research ◽

10.1016/j.exer.2005.06.022 ◽

2006 ◽

Vol 82 (2) ◽

pp. 282-292 ◽

Cited By ~ 44

Author(s):

Wei Li ◽

Hua He ◽

Tetsuya Kawakita ◽

Edgar M. Espana ◽

Scheffer C.G. Tseng

Keyword(s):

Amniotic Membrane ◽

Interferon Γ ◽

Activated Macrophages

Download Full-text

In vitro immunomodulatory effects of Astragalus verus Olivier. (black milkvetch): an immunological tapestry in Kurdish ethnomedicine

Comparative Clinical Pathology ◽

10.1007/s00580-011-1365-6 ◽

2011 ◽

Vol 22 (1) ◽

pp. 29-39 ◽

Cited By ~ 2

Author(s):

Gholamreza Nikbakht-Brujeni ◽

Hassan Tajbakhsh ◽

Mehrdad Pooyanmehr ◽

Isaac Karimi

Keyword(s):

Immunomodulatory Effects

Download Full-text

The in vitro immunomodulatory effects of sulfasalazine on human polymorphonuclear leukocytes, mononuclear cells, and cultured glomerular mesangial cells

Life Sciences ◽

10.1016/s0024-3205(00)00708-6 ◽

2000 ◽

Vol 67 (10) ◽

pp. 1149-1161 ◽

Cited By ~ 4

Author(s):

Chang-Youh Tsai ◽

Tsai-Hung Wu ◽

Chia-Li Yu ◽

Chung-Tei Chou

Keyword(s):

Polymorphonuclear Leukocytes ◽

Mononuclear Cells ◽

Mesangial Cells ◽

Glomerular Mesangial Cells ◽

Immunomodulatory Effects ◽

Human Polymorphonuclear Leukocytes

Download Full-text

Immunomodulatory Effects of Tyrosine Kinase Inhibitor In Vitro and In Vivo Study

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2017.10.039 ◽

2018 ◽

Vol 24 (2) ◽

pp. 267-275 ◽

Cited By ~ 9

Author(s):

Elena Marinelli Busilacchi ◽

Andrea Costantini ◽

Nadia Viola ◽

Benedetta Costantini ◽

Jacopo Olivieri ◽

...

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Kinase Inhibitor ◽

In Vivo Study ◽

Immunomodulatory Effects

Download Full-text

IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model

Cells ◽

10.3390/cells10113101 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3101

Author(s):

Cuiping Zhang ◽

Mina Delawary ◽

Peng Huang ◽

Jennifer A. Korchak ◽

Koji Suda ◽

...

Keyword(s):

Cell Proliferation ◽

T Cell ◽

Therapeutic Potential ◽

Immune Dysregulation ◽

T Cell Proliferation ◽

Immunomodulatory Effects ◽

Freezing And Thawing ◽

Mrna Transfection ◽

Clinical Conditions

Mesenchymal stem cells (MSCs) are used in various studies to induce immunomodulatory effects in clinical conditions associated with immune dysregulation such as graft versus host disease (GvHD). However, most of these clinical trials failed to go beyond early phase 2 studies because of limited efficacy. Various methods have been assessed to increase the potency of MSCs. IL-10 is an anti-inflammatory cytokine that is known to modulate immune responses in GvHD. In this study, we evaluated the feasibility of transfecting IL-10 mRNA to enhance MSC therapeutic potential. IL-10 mRNA engineered MSCs (eMSCs-IL10) maintained high levels of IL-10 expression even after freezing and thawing. IL-10 mRNA transfection did not appear to alter MSC intrinsic characteristics. eMSCs-IL10 significantly suppressed T cell proliferation relative to naïve MSCs in vitro. In a mouse model for GvHD, eMSCs-IL10 induced a decrease in plasma level of potent pro-inflammatory cytokines and inhibited CD4+ and CD8+ T cell proliferation in the spleen. In summary, our studies demonstrate the feasibility of potentiating MSCs to enhance their immunomodulatory effects by IL-10 mRNA transfection. The use of non-viral transfection may generate a safe and potent MSC product for treatment of clinical conditions associated with immune dysregulation such as GvHD.

Download Full-text