The MHC class‐II and CD44 molecules are involved in the induction of tumour necrosis factor (TNF) gene expression by human monocytes stimulated with tumour cells

Abstract

Tumour necrosis factor alpha (TNF) mRNA is detected in the macrophage infiltrate surrounding the tumour, but the cellular/molecular interactions leading to TNF gene expression in macrophages are unknown. The in vitro system in which human blood monocytes are stimulated with human cancer cells for TNF release was used to study such interactions. Monoclonal antibodies (MAbs) against various adhesion molecules (LFA-1, LFA-3, ICAM-1, VNR, VLA beta I chain) were unable to block TNF production in co-culture of monocytes with a human pancreatic carcinoma (HPC) cell line. However, anti-CD44 and anti-HLA-DR MAbs effectively blocked TNF release and TNF-mRNA induction in monocytes. Pre-incubation of monocytes with anti-HLA-DR and tumour cells with anti-CD44 MAbs had a similar effect. It was concluded that CD44 molecules are involved in tumour-monocyte interactions and that HLA-DR determinants of monocytes are engaged in signal transduction for TNF gene activation. These findings may suggest that certain surface determinants of tumour cells act as ligands for MHC class-II molecules and induce TNF production in monocytes.

Anti-TNF Antibody Modulates Cytokine and MHC Expression in Cardiac Allografts

“…TNF probably participates in the inductive phases of the immune response by increasing cellular expression of MHC class I and class II [12]. Furthermore, the mechanism of action by which many cytokines, including TNF, alter and affect class II MHC gene expression has been extensively studied [22,23]. Additionally, TNF has been postulated to alter cytokine profiles to a T helper 1-like response, which was confirmed by this present study.…”

Hypercholesterolemia-Induced Long-Term Increase of Macrophages in the Myocardium of New Zealand White Rabbits

“…Quantification of the CD44 expression on mononuclear cells revealed that low-density lipoprotein adsorption therapy significantly reduced this receptor [Uno et al, 1995]. Hypothesizing that there is a contrary effect in our experiments, as a response to an elevation of the cholesterol levels an increased expression of CD44-dependent genes, such as TNF, might be a consequence [Zembala et al, 1994] as well as the corresponding release of the gene product [Jovinge et al, 1996]. TNF is a proinflammatory cytokine and mediator of oxidative stress and is capable to contribute to an upregulation of MnSOD in the interstitial DC and M∑ [Wong and Goeddel, 1988;Brennan et al, 1999;Kinscherf et al, 1999;Mikecz et al, 1999].…”

miR-200c affects the mRNA expression of E-cadherin by regulating the mRNA level of TCF8 during post-natal epididymal development in juvenile rats

“…E-cadherin is a cell surface protein that mediates intercellular adhesion and is involved in adherence, gap, and tight junctions between epithelial cells, which results in the formation and maintenance of blood-epididymal barrier [16]. Interleukin-2 is a cytokine playing a role in activating macrophages that can carry out endocytosis to prevent microbial infection and eliminate senescent cells [17].…”

“…Park et al [15] also reported that miR-200c can target the E-cadherin repressor, TCF8, so that it can determine the epithelial phenotype of cancer cells as E-cadherin is involved in epithelial-tomesenchymal transition. As known, E-cadherin is a junctional protein and interleukin-2 is a cytokine that can activate macrophages concerning endocytosis [16,17]. It was also revealed that these two kinds of molecules are related to post-natal epididymal development in the rat [11].…”