IGF-I protects human oral buccal mucosal epithelial cells from sodium nitroprusside-induced apoptosis via PI3-kinase.

Objective: Cancers of the head and neck account for the vast majority of all malignancies of the oral cavity. The insulin-like growth factor (IGF) family of proteins is well documented to have an important role in rescuing cells from apoptosis. While it is known the IGF proteins are present in normal oral epithelial and cancer cells its role is not fully understood.

Upregulation of IGF-2 and IGF-1 receptor expression in oral cancer cell lines.

The insulin-like growth factors (IGFs) are a family of mitogenic proteins involved in the regulation of cell growth and differentiation. The presence and role of the IGF system in oral mucosal epithelium is not clear but could influence our understanding of the pathogenesis of oral cancer. We characterised the expression and function of IGF-1, IGF-2 and IGF receptor in human oral squamous carcinoma cell lines and normal oral epithelial cells as well as normal oral and squamous cell carcinoma tissues.

Serum levels of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs), -1, -2, -3, in oral cancer.

Introduction: Insulin-like growth factor (IGF) possesses mitogenic properties promoting cellular proliferation and inhibiting cellular apoptosis. Reported evidence suggests that cancer (non-oral) is associated with high circulating levels of IGF-1 and low levels of IGFBP-3.

Aims: This study measured circulating levels of IFG-1 and IGFBPs -1, -2 and -3 in oral cancer patients.

Adrenomedullin increases the expression of calcitonin-like receptor and receptor activity modifying protein 2 mRNA in human microvascular endothelial cells.

Adrenomedullin (AM) is a multifunctional peptide hormone, which plays a significant role in vasodilation and angiogenesis, implicating it in hypertension as well as in carcinogenesis. AM exerts its effects via the calcitonin receptor-like receptor (CRLR, now known as CL) complexed with either receptor activity modifying protein (RAMP) 2 or 3. We have investigated the effect of AM on immortalized human microvascular endothelial cells 1, since endothelial cells are a major source as well as a target of AM actions in vivo.

Differentiation of the HaCaT keratinocyte cell line: modulation by adrenomedullin.

Background: Adrenomedullin (AM) is a multifunctional peptide produced by a wide variety of cells, including keratinocytes. We, and others, have demonstrated that AM has a role as a growth regulatory factor of the skin and contributes as an antimicrobial agent in the integument's protective barrier. It is not known whether AM has a role in differentiating keratinocytes.

Mechanisms of adrenomedullin antimicrobial action.

The mechanism of antimicrobial action of the multifunctional peptide adrenomedullin (AM) against Escherichia coli and Staphylococcus aureus was investigated. AM (52 residues) and AM fragments (1-12, 1-21, 13-52, 16-21, 16-52, 22-52, 26-52 and 34-52 residues) were tested for activity. Carboxy-terminal fragments were shown to be up to 250-fold more active than the parent molecule.

A human oral keratinocyte cell line responds to human heat shock protein 60 through activation of ERK1/2 MAP kinases and up- regulation of IL-1beta.

Heat shock proteins (HSP) are released by cells in response to stress signals. It is hypothesized that pathogenic bacteria stimulate the cells in the periodontium to up-regulate the expression of HSP60, which would stimulate macrophages, and possibly other cells, to produce proinflammatory cytokines. We sought to determine whether oral keratinocytes responded to recombinant human HSP60 and to identify the signalling pathways involved.

Integrin expression in developing human salivary glands.

The development and complete differentiation of salivary glands is a complex process that involves a large number of co-ordinated events. Little is known about the molecular basis for salivary gland development. However, we have reported previously that integrins appear to play a role.

Presentation of ICAM-1 protein at the cell surface of oral keratinocytes in the presence of adrenomedullin and corticotrophin.

Increasing evidence suggests that adrenomedullin (AM) and corticotrophin (ACTH) are immunomodulatory. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the recruitment of leukocytes not only from peripheral blood into inflamed tissues but also into epithelia. We have investigated the effects of AM and ACTH on the expression of ICAM-1 by human oral keratinocytes.

Adrenomedullin signals through NF-kappaB in epithelial cells.

Adrenomedullin is a peptide found in a variety of cells and tissues and involved in a multitude of biological processes. Recently, adrenomedullin has been identified as a host defense peptide and as such it plays a role in the inflammatory response. The transcription factor NF-kappaB is a major regulator of genes involved in the inflammatory response and the aim of this study was to determine whether NF-kappaB played a role in the inflammatory process triggered by adrenomedullin.

Expression patterns of integrins on pleomorphic adenoma and adenoid cystic carcinoma: study on specimens and in vitro investigation of the effects of extracellular matrix on the expression of these adhesion molecules.

Background: Pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) are neoplasms of distinct behaviour, showing similar origin, cell components and marked presence of extracellular matrix (ECM). Interactions between cells and ECM are important in the biology of tumours, being partially mediated by integrins. This study investigated these interactions on PA and ACC using paraffin-embedded tissue and an in vitro model of these conditions.

Expression of adrenomedullin and its receptors in human salivary tissue.

Adrenomedullin is a multifunctional peptide produced by a wide range of different cells and tissues. This study was designed to investigate whether adrenomedullin is present in human saliva and in salivary glands. It was expected that saliva may contain high concentrations of adrenomedullin, which has antimicrobial activity in vitro, which may have functional implications in the oral cavity.

Stimulation of adhesion molecule expression in human endothelial cells (HUVEC) by adrenomedullin and corticotrophin.

Adrenomedullin (AM) and corticotrophin (ACTH) are both vasoactive peptides produced by a variety of cell types, including endothelial cells. Although AM and ACTH are considered to be important in the control of blood pressure and the response to stress, respectively, their role in inflammation and the immune response has not been clarified. This study shows, with the use of a cell-based ELISA, that AM and ACTH induce cell surface expression of the adhesion molecules E-selectin, VCAM-1, and ICAM-1 on human umbilical vein endothelial cells (HUVEC).

Adrenomedullin expression by gastric epithelial cells in response to infection.

Many surface epithelial cells express adrenomedullin, a multifunctional peptide found in a wide number of body and cell systems. Recently, we and others have proposed that adrenomedullin has an important novel role in host defense. This peptide has many properties in common with other cationic antimicrobial peptides, including the human beta-defensins.

Salivary gland tumours: immunoexpression of integrins beta 1, beta 3 and beta 4.

Background: Integrins, heterodimeric transmembranic adhesion molecules composed of alpha and beta subunits, have been implicated in normal and neoplastic biological processes. We investigated the patterns of expression of integrins subunits beta 1, beta 3 and beta 4 in neoplasms derived from the terminal segment of salivary glands in order to understand their expression patterns in the different structures of these tumours.

Methods: Immunohistochemistry using 'catalized signal amplification' (CSA) detection system was applied to paraffin-embedded specimens of polymorphous low-grade adenocarcinoma, adenoid cystic carcinoma and acinic cell carcinoma.

Adrenomedullin and mucosal defence: interaction between host and microorganism.

Many surface epithelial cells express adrenomedullin (AM) and it is postulated that it may have an important protective role. This peptide has many properties in common with other cationic antimicrobial peptides including the human beta-defensins. Antimicrobial activity against members of the human skin, oral, respiratory tract and gastric microflora has been demonstrated.

Paracrine effects of PAMP and adrenomedullin on the human adrenal H295R cell line: PAMP but not adrenomedullin stimulates DHEA secretion.

It has previously been shown, by this laboratory and others, that adrenal cells actively secrete adrenomedullin. Here it is demonstrated that human adrenal cells also secrete the related peptide, proadrenomedullin N-terminal 20 peptide (PAMP). The actions of adrenomedullin and PAMP on adrenal steroid secretion were determined by measuring the aldosterone, cortisol and dehydroepiandrosterone (DHEA) content of cell culture medium after exposure of the human adrenal H295R cells to either PAMP or adrenomedullin.

Adrenomedullin: expression and possible role in human skin and hair growth.

Background: Adrenomedullin (AM) is a regulatory peptide that is synthesized and secreted by a wide number of cells and tissues. AM is a potent vasodilator, but also exerts other functions, such as regulating cell growth and antimicrobial defence. Two receptors, L1 and calcitonin receptor-like receptor (CRLR), which are able to bind AM, have been cloned and characterized.

Adrenomedullin in the adrenal.

Adrenomedullin (AM) was originally characterized in extracts of an adrenal medullary tumor. Since this original finding the peptide and its mRNA have also been found in the adrenal cortex, specifically, in the cells of the aldosterone-secreting zona glomerulosa. It is clear that the synthesis of AM is actively regulated in both cortex and medulla.

Adrenomedullin and calcitonin gene-related peptide receptors in the rat adrenal cortex.

The actions of calcitonin gene-related peptide (CGRP) and adrenomedullin on steroid hormone secretion from the rat zona glomerulosa are controversial, with reports in the literature of both stimulatory and inhibitory effects. It appears that these results previously obtained may depend on the nature of the receptors expressed by zona glomerulosa cells. The present study was designed to characterize CGRP and adrenomedullin binding in the rat adrenal zona glomerulosa.

Regulation of rat adrenal vasoactive intestinal peptide content: effects of adrenocorticotropic hormone treatment and changes in dietary sodium intake.

Vasoactive intestinal peptide (VIP) is well established as a paracrine regulator of adrenal function. It is present in nerves supplying the adrenal cortex, although previous studies have found that the amount of VIP in the outer zones of the rat adrenal is not affected by ligating the splanchnic nerve supplying the adrenal gland. The present studies were designed to investigate the mechanisms involved in regulating the VIP content of the rat adrenal gland.

Adrenomedullin expression in pathogen-challenged oral epithelial cells.

Adrenomedullin, a multifunctional peptide, is expressed by many surface epithelial cells and, previously, we have demonstrated that adrenomedullin has antimicrobial activity. The oral cavity contains an epithelium that is permanently colonized by microflora, yet infections in a host are rare. We exposed oral keratinocytes to whole, live cells from four microorganisms commonly isolated from the oral cavity, Porphyromonas gingivalis, Streptococcus mutans, Candida albicans and Eikenella corrodens.

Regulation of adrenomedullin secretion in cultured human skin and oral keratinocytes.

Adrenomedullin, a potent vasoactive peptide, is actively secreted from primary cultures of human oral and skin keratinocytes, but nothing is known of the regulation of its release. This study describes the effects of a range of substances on adrenomedullin production from cultures of oral and skin keratinocytes. We have established that keratinocytes do not store adrenomedullin but secrete it constitutively.

Autocrine role of adrenomedullin in the human adrenal cortex.

Previous studies from our laboratory have reported that adrenomedullin is synthesised in rat zona glomerulosa cells. In the present studies, it was found that the human adrenocortical cell line H295R expresses the gene encoding adrenomedullin, and that immunoreactive adrenomedullin is released into the culture medium. Furthermore, it was found that secretion of adrenomedullin is regulated by angiotensin II and forskolin.

Aldosterone secretion by the rat adrenal cortex is stimulated by the activation of protease-activated receptor 1.

Stimulation of aldosterone by a serine protease, trypsin, was first reported in 1982, although the mechanism of this effect was unclear. Recently, a family of protease-activated receptors (PARs) has been described and four members of the family characterised and cloned, including the previously recognised thrombin receptor. This study investigated whether PARs mediate the action of trypsin on aldosterone secretion.