Role of CD154 in cancer pathogenesis and immunotherapy

Hassan, Ghada S.; Stagg, John; Mourad, Walid

doi:10.1016/j.ctrv.2015.03.007

Cited by 24 publications

(26 citation statements)

References 114 publications

(132 reference statements)

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“…It has been reported that the activation of CD40 leads to the expression of CD80/CD86 and the production of IL-12, thus intensifying T cell costimulation and skewing Th1/Th2 responses (37). Hassan et al (38) suggested that the level of CD40L/CD40 signaling was the determinant of a tilt to a pathogenic role or a protective role. It has also been shown that TLR9-mediated inflammation triggers alveolar bone loss in experimental murine periodontitis (39).…”

Section: Local B Cell Il-10 Induction Alleviates Periodontitismentioning

confidence: 99%

Local Induction of B Cell Interleukin-10 Competency Alleviates Inflammation and Bone Loss in Ligature-Induced Experimental Periodontitis in Mice

Hu²,

Liu

et al. 2017

Infect Immun

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Interleukin-10 (IL-10)-producing B cells (B10 cells) play a critical role in the immune system balance by negatively regulating inflammatory responses. This study was conducted to determine the effect of local B10 cell induction on periodontal inflammation and bone loss in ligature-induced experimental periodontitis in vivo. Purified spleen B cells from C57BL/6J mice (8 to 10 weeks old) were cultured with CD40 ligand (CD40L) and the Toll-like receptor 9 (TLR9) agonist cytidinephosphate-guanosine oligodeoxynucleotide (CpG) to determine effective IL-10 induction in vitro. Silk ligatures (size 7-0) were tied around the mouse maxillary second molars on day 0, followed by the injection of CD40L and CpG into the palatal gingiva on days 3, 6, and 9. All the mice were sacrificed, and samples were collected on day 14. CD40L and CpG significantly increased the level of IL-10 production by B cells in vitro, although the frequencies of CD1d hi CD5 ϩ and IL-10-producing (IL-10 ϩ ) CD45 ϩ cells were decreased. IL-10 was predominantly produced by the CD1d hi CD5 ϩ subpopulation of B cells. In vivo, both IL-10 mRNA expression and the number of IL-10 ϩ CD45 ϩ cells were significantly increased after gingival injection of CD40L and CpG. Periodontal bone loss was significantly decreased and the gingival expression of IL-1␤, tumor necrosis factor alpha, and RANKL was significantly reduced. The number of multinucleated tartrate-resistant acid phosphatase-positive cells along the alveolar bone surface was significantly decreased after gingival injection of CD40L and CpG. This study indicates for the first time that the local induction of B10 cell activity could inhibit periodontal inflammation and bone loss. 1-4). One of the most widely studied Breg subsets is termed interleukin-10 (IL-10)-producing B cells (B10 cells) (5) due to their pivotal capability to produce the anti-inflammatory cytokine IL-10. Currently, due to the lack of unique phenotypic markers, these IL-10-competent B cells are functionally identified by their production of IL-10 (6). Spleen B10 cells are predominantly enriched within the CD1d hi CD5 ϩ subpopulation, where among them more than 50% are competent to express 7). Although the frequency is low (1 to 3% of splenic B cells in mice and less than 1% of circulating B cells in humans), there is emerging evidence demonstrating that a deficiency of B10 cells exacerbates the

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Section: Local B Cell Il-10 Induction Alleviates Periodontitismentioning

confidence: 99%

Local Induction of B Cell Interleukin-10 Competency Alleviates Inflammation and Bone Loss in Ligature-Induced Experimental Periodontitis in Mice

Hu²,

Liu

et al. 2017

Infect Immun

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“…CD40 is a 45-50 kDa phosphorylated type I integral membrane glycoprotein that belongs to the tumor necrosis factor receptor superfamily, which is expressed on various hematopoietic and non-hematopoietic cells (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). CD40 is involved in several biological functions, such as cell-mediated immunity and cell growth regulation.…”

Section: Introductionmentioning

confidence: 99%

“…Through interaction with its receptor, CD154 is pivotal in T-cell-dependent humoral response and cell-mediated immunity and inflammation. Thus, it is a key element in the pathogenic process of chronic inflammatory diseases and autoimmune disorders and has additional implications for the many pathogenic steps of tumorigenesis (10,12,13).…”

Section: Introductionmentioning

confidence: 99%

Immune receptors CD40 and CD86 in oral keratinocytes and implications for oral lichen planus

et al. 2017

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Lichen planus (LP) is a chronic T-cell-mediated mucocutaneous inflammatory disease that targets stratified epithelia, including those lining the oral cavity. The intraoral variant of LP (OLP) is associated with interferon (IFN)-γ production by infiltrating T lymphocytes; however, the role of epithelial cells in the etiopathogenesis OLP is not completely understood. There is however a growing body of evidence regarding the involvement of epithelial-derived cytokines, immune receptors, and costimulatory molecules in the pathobiological processes that promote and sustain OLP. In the present study, we used a reverse transcriptase-polymerase chain reaction assay to assess whether CD40-a receptor found mainly on antigen presenting cells-and the costimulatory molecule CD86 were expressed in oral keratinocytes (three strains of primary normal oral keratinocytes and the H357 cell line) in the presence or absence of IFN-γ. To further characterize the involvement of CD40 in OLP, expression and distribution of receptor and ligand (CD40/CD154) in tissues from OLP were evaluated by immunohistochemistry. The present results are the first to show that both CD40 and CD86 are constitutively expressed at low levels in oral keratinocytes and that their expression was enhanced by IFN-γ stimulation. The intensity of CD40 staining in OLP tissues was strong. Taken together, the results strongly suggest that CD40 and CD86 play a role in the pathophysiology of oral inflammatory diseases such as OLP.

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“…CD40 ligand (CD40L), otherwise known as CD154, is a 33-kDa type II transmembrane protein expressed on the membranes of T lymphocytes, and belongs to the tumor necrosis factor superfamily (6). CD40 is the CD40L receptor, and is expressed on the membranes of B lymphocytes and macrophages (7).…”

Section: Introductionmentioning

confidence: 99%

Raised CD40L expression attenuates drug resistance in Adriamycin‑resistant THP‑1 cells

Feng

Chen

2020

Exp Ther Med

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Acute myeloid leukemia is a common hematological malignancy that often exhibits strong drug resistance when treated using conventional chemotherapy. Although numerous studies have been carried out to develop methods of overcoming drug resistance, the results have generally been unsatisfactory. CD40 ligand (CD40L) has been shown to improve the sensitivity of cancer cells to drug treatment. In the present study, Adriamycin (ADM)-resistant human monocytic THP-1 cells (THP-1/A cells) were developed by incubating THP-1 cells with increasing concentrations of ADM. Cells were transfected with CD40L vectors to explore the potential involvement of CD40L in regulating multidrug resistance (MDR) in cancer. Cell proliferation and viability were measured using the Cell Counting Kit-8 assay; cell apoptosis was evaluated by flow cytometry, trypan blue staining and caspase-3 activity; and the expression of MDR-associated protein 1 (MRP1) and permeability glycoprotein (P-gp) was analyzed using western blotting. The results revealed that the protein expression levels of MRP1 and P-gp were downregulated by raised CD40L expression and that the combination of raised CD40L expression with daunorubicin (DNR), a drug from which ADM is derived, significantly increased the extent of cell apoptosis, indicating that drug resistance was effectively attenuated by CD40L. Collectively, these results suggested that CD40L may contribute towards reducing DNR resistance in THP-1/A cells.

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Role of CD154 in cancer pathogenesis and immunotherapy

Cited by 24 publications

References 114 publications

Local Induction of B Cell Interleukin-10 Competency Alleviates Inflammation and Bone Loss in Ligature-Induced Experimental Periodontitis in Mice

Local Induction of B Cell Interleukin-10 Competency Alleviates Inflammation and Bone Loss in Ligature-Induced Experimental Periodontitis in Mice

Immune receptors CD40 and CD86 in oral keratinocytes and implications for oral lichen planus

Raised CD40L expression attenuates drug resistance in Adriamycin‑resistant THP‑1 cells

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