Up-Regulation of CD44 Expression by Tumor Necrosis Factor-α Is Neutralized by Interleukin-10 in Langerhans Cells

Osada, Atsushi; Nakashima, Hideki; Furue, Masutaka; Tamaki, Kunihiko

doi:10.1111/1523-1747.ep12313437

Cited by 34 publications

(22 citation statements)

References 19 publications

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“…Therefore, the expression of CD44-variants might be differently regulated from that of the standard form of CD44, and commonly independent of LMP1-expression in epithelial malignancies associated with EBV. It is possible that EBV infection may influence CD44-expression by interacting with cytokine genes, such as those for TNFa, IFNg and interleukin 10, which are known to modulate CD44-expression (Mackay et al, 1994;Osada et al, 1995). In the present study, the magnitude of CD44-variant expression at the protein level was also correlated with lymph node metastasis.…”

Section: Discussionsupporting

confidence: 50%

Expression of CD44 variants in gastric carcinoma with or without Epstein-Barr virus

et al. 1997

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The significance of CD44 variants in gastric carcinoma has not been fully investigated in terms of the pathological features of the carcinoma, including its association with Epstein-Barr virus (EBV). In this study, a total of 104 primary gastric carcinoma tissues (EBV-associated gastric carcino-mas, EBVaGC, and EBV-negative carcinomas) were evaluated by immunohistochemistry. When the immunoreactivity of formalin-fixed, paraffin-embedded sections was graded on a scale of 0-3, the frequencies of grades 0-1, 2 and 3 were, respectively, 77%, 16% and 7% using monoclonal antibody (MAb) 3G5, which recognizes V3-5, and 70%, 14% and 15% with MAb 2F10, which recognizes V6. The expression of CD44 variants is independently correlated with lymph node metastasis and EBV-association in gastric carcinoma. Significant correlations were observed between V3-5 expression and lymph vessel invasion or lymph node metastasis, and between V6 expression and lymph node metastasis. The expression of both variants was significantly correlated with EBV-association. EBV-association and lymph node metastasis contributed independently to CD44 variant expression by multivariate analysis. Thus, the mechanism and significance of CD44 variant-expression are different in gastric carcino-mas with or without EBV. EBVaGC is a distinct type of gastric carcinoma which should be considered separately from EBV-negative carcinoma. Int.

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Section: Discussionsupporting

confidence: 50%

Expression of CD44 variants in gastric carcinoma with or without Epstein-Barr virus

et al. 1997

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“…The association of CD44 with inflammation was further supported by some in vitro studies in which CD44 was upregulated by some inflammatory cytokines on various cell types such as NK cells,25 epidermal Langerhans cells,26endothelial cells, myelomonocytic cell lines, and some epithelial cell lines 427 It seems likely that the CD44 regulation is disease and isoform specific, as suggested by Rosenberg and colleagues 28.…”

Section: Discussionmentioning

confidence: 84%

Expression of adhesion molecule CD44 on human corneas

Zhu¹,

Nölle²,

Duncker³

1997

British Journal of Ophthalmology

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Aims-This study was undertaken to confirm the distribution and expression of the molecule CD44 on human corneas under normal and pathological conditions. Methods-Fifty eight corneal buttons from adult patients suVering from various corneal diseases and four normal corneas were included in this study. Frozen sections were stained immunohistochemically with monoclonal antibodies against human CD44 using an APAAP method and observed under a light microscope. Results-In normal corneas CD44 was predominantly expressed on the membranes of basal epithelial cells and on the keratocytes, as well as on the vascular endothelial cells of the corneal limbi, but was not expressed on corneal endothelial cells. Enhanced expression of CD44 was observed on the epithelium of corneas with inflammation and allograft rejection. In a number of abnormal conditions including allograft rejection, corneal trauma, primary and secondary corneal endothelial decompensation the remaining endothelial cells stained positively for CD44. However, in some corneas of keratitis, keratoconus, and dystrophy the endothelium which appeared relatively integral in morphology and amount remained CD44 negative. Conclusions-These results suggest that CD44, the hyaluronate receptor, may play an important role in corneal cell-cell and cell-matrix interactions. Its regulation is closely related to corneal inflammatory reactions. The induction of CD44 on corneal endothelium might play a potential role in compensatory processes when corneal endothelial cells are injured. (Br J Ophthalmol 1997;81:80-84) CD44, the hyaluronate receptor, 1 is a transmembrane glycoprotein which was recognised as a cell adhesion receptor that takes part in cell-cell and cell-matrix interaction such as cell migration, lymphocyte homing and activation, and tumour growth and metastasis.2-4 The main haematopoietic form of CD44 has a molecular weight of 85-95 kDa.5 6 There are some variant CD44 isoforms (CD44v) induced by alternate splicing of multiple exons into the extracellular domain and by diVerent post-translational modifications in diVerent cell types.3 7 CD44 may bind its ligand hyaluronan in response to antigenic stimuli and may participate in the eVector stage of immunological responses, 8 and be capable of binding fibronectin, laminin, and collagen I. 6 9 In corneal disorders such as keratitis and corneal allograft rejection some cell adhesion molecules have been shown to be involved in the pathological processes. [10][11][12][13] However, whether CD44 participates in the processes of corneal diseases is less well known. There have been very few studies of CD44 in human corneas and the existing reports on the distribution of CD44 on corneal tissues diVer. Alho and Underhill reported that CD44 was absent from human corneal epithelium, 14 and Foets and colleagues showed that corneal endothelial cells were negative for CD44, but also reported a 'garland-like' positive pattern of expression in corneal endothelial flat mounts of organ cultured corneas. 15 However, on rabb...

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“…This concept was originally derived from the observations that 1) CD44 expression is detectable on epidermal LC in normal skin (50,51); 2) LC elevate surface expression of selected CD44 isoforms upon hapten painting (47); and 3) antagonistic anti-CD44 mAb and Pep-1 both inhibit LC migration from the epidermis and the subsequent contact hypersensitivity responses (29,47,52). More recent reports, however, do not necessarily support the above view.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Surface Expression of Hyaluronan by Dendritic Cells and Its Potential Role in Antigen Presentation

Mummert

Edelbaum

et al. 2002

The Journal of Immunology

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Hyaluronan (HA) is a large glycosaminoglycan consisting of repeating disaccharide units of glucuronic acid and N-acetylglucosamine. HA is known to act as a filling material of extracellular matrices and as an adhesive substrate for cellular migration. Here we report that dendritic cells (DC) express mRNAs for HA synthases and hyaluronidases, actively synthesize HA, and display HA on their surfaces. Interestingly, HA expression levels on DC were not significantly altered by their maturation states. With respect to physiological function, three specific HA inhibitors, i.e., bovine proteoglycan, a 12-mer HA-binding peptide (GAHWQFNALTVR) termed Pep-1, and an oligomeric Pep-1 formulation, all interfered with DC-induced activation of CD4+ T cells isolated from DO11.10 TCR transgenic mice. For example, Pep-1 oligomer efficiently inhibited DC-dependent cluster formation, IL-2 and IFN-γ production, and proliferation by DO11.10 T cells in vitro without affecting the viabilities of DC or T cells, DC function to uptake exogenous proteins, or DC-T cell conjugate formation at earlier time points. These observations suggest a paracrine mechanism by which DC-associated HA facilitates some of the late changes in T cell activation. Although T cells constitutively expressed mRNAs for HA synthases and hyaluronidases, their surface HA expression became detectable only after activation. Oligomeric Pep-1 and bovine proteoglycan both inhibited mitogen-triggered T cell activation in the absence of DC, suggesting an autocrine mechanism by which HA expressed by T cells assists their own activation processes. Finally, adoptively transferred DO11.10 T cells showed progressive mitosis when stimulated with Ag-pulsed DC in living animals, and this clonal expansion was inhibited significantly by administration of Pep-1 oligomer. Our findings may introduce a new concept that relatively simple carbohydrate moieties expressed on DC and perhaps T cells play an important immunomodulatory role during Ag presentation.

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Up-Regulation of CD44 Expression by Tumor Necrosis Factor-α Is Neutralized by Interleukin-10 in Langerhans Cells

Cited by 34 publications

References 19 publications

Expression of CD44 variants in gastric carcinoma with or without Epstein-Barr virus

Expression of CD44 variants in gastric carcinoma with or without Epstein-Barr virus

Expression of adhesion molecule CD44 on human corneas

Synthesis and Surface Expression of Hyaluronan by Dendritic Cells and Its Potential Role in Antigen Presentation

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