Human epidermis and epithelium serve as physiologic barriers to protect against noxious and infectious agents. Contributing to the defense against infection, epithelial cells express antimicrobial peptides (AMPs). The expression of AMPs in keratinocytes is generally regulated directly by bacteria and indirectly by proinflammatory cytokines. Bacteria may also regulate AMP expression by inducing keratinocyte expression of the autonomous proinflammatory cytokine, interleukin-1a (IL-1a). To test the hypothesis that AMP expression may be regulated by cell autonomous cytokines, we investigated the effect of IL-1a on the expression of AMPs in human keratinocytes (HaCaT cells) by microarray, northern blot, reverse transcriptase (RT)-PCR and western blot analyses. IL-1a increased expression of mRNA in a dose-and time-dependent manner specific for lipocalin 2, S100A8, S100A9 and secretory leukocyte protease inhibitor (SLPI) more than twofold relative to nonstimulated cells (control), and slightly upregulated S100A7 and b-defensin-2. Furthermore, the expression of lipocalin 2, S100A7, S100A8, S100A9 and SLPI proteins were upregulated by IL-1a. On the other hand, HaCaT cells expressed mRNA specific for other AMPs, including cystatin 3, adrenomedullin, RNase-7 and mucin 5, which were unaffected by IL-1a treatment. These results suggest that the autonomous keratinocyte cytokine, IL-1a, selectively upregulates the expression of AMPs which may modulate innate epithelial cell immunity in skin and mucosa.
To establish a tool to study ghrelin production and secretion in vitro, we developed a novel ghrelin-producing cell line, MGN3-1 (mouse ghrelinoma 3-1) cells from a gastric ghrelin-producing cell tumor derived from ghrelin-promoter Simian virus 40-T-antigen transgenic mice. MGN3-1 cells preserve three essential characteristics required for the in vitro tool for ghrelin research. First, MGN3-1 cells produce a substantial amount of ghrelin at levels approximately 5000 times higher than that observed in TT cells. Second, MGN3-1 cell expressed two key enzymes for acyl modification and maturation of ghrelin, namely ghrelin O-acyltransferase for acylation and prohormone convertase 1/3 for maturation and the physiological acyl modification and maturation of ghrelin were confirmed. Third, MGN3-1 cells retain physiological regulation of ghrelin secretion, at least in regard to the suppression by somatostatin and insulin, which is well established in in vivo studies. Thus, MGN3-1 cells are the first cell line derived from a gastric ghrelin-producing cell preserving secretion of substantial amounts of ghrelin under physiological regulation. This cell line will be a useful tool for both studying the production and secretion of ghrelin and screening of ghrelin-modulating drugs.
Multiple protein components in gingival crevicular fluid were analysed at the same time using mass spectrometry, and this approach may be useful for the diagnosis of periodontal diseases.
Elevated plasma brain natriuretic peptide (BNP) levels have been described in patients with congestive heart failure and acute myocardial infarction. We measured plasma BNP levels in patients with chronic respiratory failure to evaluate the correlation between plasma BNP levels and pulmonary haemodynamics. Plasma BNP levels were measured in 28 patients with chronic respiratory failure accompanied by three underlying diseases [14 with chronic obstructive pulmonary disease (COPD), seven with sequelae of pulmonary tuberculosis (sequelae Tbc) and seven with diffuse panbronchiolitis (DPB)] by immunoradiometric assay methods (IRMA). Twenty-one of 28 patients had already received oxygen supplementation and 16 of 21 patients were treated as outpatients with home oxygen therapy. Plasma BNP levels were significantly elevated in patients with chronic respiratory failure complicated by cor pulmonale (81.5 +/- 13.1 pg ml-1) compared to patients without cor pulmonale (13.3 +/- 2.7 pg ml-1, P < 0.001). As controls, plasma BNP levels in 10 patients with primary lung cancer were studied, and the results (3.5 +/- 1.0 pg ml-1) were not significantly different from those of patients with chronic respiratory failure without cor pulmonale. Plasma BNP levels in 12 healthy subjects were also studied, and the results (7.2 +/- 1.0 pg ml-1) were not significantly different from those of the control subjects. Plasma BNP levels showed a weak linear correlation with systolic pulmonary arterial blood pressure, estimated by Doppler echocardiography (r = 0.43; P = 0.068), but there was no significant correlation between BNP levels and the degree of hypoxaemia (r = 0.30; P = 0.138). Plasma atrial natriuretic peptide (ANP) levels in patients with chronic respiratory failure were also measured using the same samples. Plasma ANP levels were also significantly elevated in patients with chronic respiratory failure complicated by cor pulmonale (80.8 +/- 12.1 pg ml-1) compared to patients without cor pulmonale (26.1 +/- 4.4 pg ml-1, P = 0.003). A significant correlation was found between plasma BNP and ANP levels (r = 0.68; P < 0.001). Our results suggest that the plasma BNP or ANP level may be a useful indicator for detecting the presence of cor pulmonale in patients with chronic respiratory failure.
AGEs increase IL-6 and ICAM-1 expression via the RAGE, MAPK and NF-κB pathways in HGFs and may exacerbate the progression of the pathogenesis of periodontal diseases.
We show, for the first time, the presence of resistin in gingival crevicular fluid. A high resistin level in gingival crevicular fluid samples from periodontitis patients may to some extent be related to P-LPS-induced resistin release from neutrophils.
The 6MW stress echocardiography noninvasively provides an incremental prognostic value of PH development in CTD. This is a single-center prospective cohort study. Larger multicenter studies are warranted to confirm this result.
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