ABSTRACT
IL-1-related cytokines share similarities in their receptor distribution and signalling pathways; however, overlapping actions of these cytokines have not been clearly demonstrated. The aim of our study was to compare the capacity of different IL-1-related cytokines to stimulate production and release of multiple CC and CXC chemokines by epithelial cells. The chemokine gene expression was studied using a cDNA array system in human alveolar type-II like cells A549 stimulated by IL-1ß, IL-18, and IL-33. The chemokine levels in culture supernatants were measured using multiplex immunoluminometric assay or by ELISA. In repetitive experiments, in response to IL-1ß epithelial cells expressed mRNA for CCL2, CCL5, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, and CXCL11. In contrast, induction of epithelial cells by IL-33 and IL-18 resulted only in moderate up-regulation of a few CC or CXC chemokines compared to the potent effect of IL-1ß stimulation. We conclude from our data that individual members of the IL-1 family, although related in molecular structure and signalling pathways, widely differ in their capacity to stimulate epithelial production of both CXC and CC chemokines.
Subject(s)
Chemokines/genetics , Epithelial Cells/metabolism , Interleukin-1/pharmacology , Lung/pathology , Cell Line, Tumor , Chemokines/metabolism , Epithelial Cells/drug effects , Gene Expression Regulation, Neoplastic/drug effects , HumansABSTRACT
Replacing SAFAs (saturated fatty acids) for vegetable PUFAs (polyunsaturated fatty acids) has a well documented positive effect on the lipoprotein pattern while the direct effect of dietary fatty acids composition on systemic inflammation remains to be proven. In well controlled randomised cross-over study with 15 overweight/obese postmenopausal women, the effect of dietary switch on systemic inflammation was investigated. A two 3 weeks dietary period either with predominant animal fat (SAFA, 29 caloric % SAFA) or vegetable fat (PUFA 25 % caloric % PUFA) were interrupted by wash-out period. The expected increasing effect on SAFA diet to LDL-C (low density cholesterol) and opposite effect of PUFA diet was documented following changes in fatty acid spectrum in VLDL (very low density cholesterol) particles. The switch from SAFA diet to PUFA diet produced a significant change of CRP (C-reactive protein) concentration (p<0.01) whereas similar trend of IL-18 did not reach statistical significance. In this study, previous in vitro results of different SAFA and PUFA proinflammatory effects with well documented molecular mechanisms were first proven in a clinical study. It could be stated that the substantial change of dietary fatty acid composition might influence proinflammatory effect in addition to traditional cardiovascular risk factors.
Subject(s)
Dietary Fats/therapeutic use , Inflammation/diet therapy , Inflammation/prevention & control , Aged , Anthropometry , Blood Glucose/metabolism , C-Reactive Protein/metabolism , Cross-Over Studies , Cytokines/blood , Diet , Fatty Acids/blood , Female , Humans , Lipoproteins, VLDL/blood , Middle Aged , Obesity/diet therapy , Overweight/diet therapy , Postmenopause , Waist CircumferenceABSTRACT
Macrophages located in airways and the alveolar space are continually exposed to different signals from the respiratory mucosa. In this respect, epithelial cells represent an important source of cytokines and mediators modulating the state of activation and/or differentiation of mononuclear phagocytes. Many of the proinflammatory genes induced in macrophages during immune and immunopathological reactions are regulated by transcription factor NF kappa B. The aim of our study was to characterize changes in the expression of genes associated with NF kappa B activation and signalling in THP-1 human macrophages co-cultured with A549 respiratory epithelial cells. At least 4-fold upregulation of mRNA level was found in 29 of 84 tested genes including genes for multiple cytokines and chemokines, membrane antigens and receptors, and molecules associated with NF kappa B signalling. The mRNA induction was confirmed at the level of protein expression by evaluating the release of IL-6 and IL-8 and by ICAM-1 expression. Blocking of one NFκB subunit by p65 siRNA inhibited the production of IL-6 in both cell types while IL-8 release from THP-1 cells did not seem to be affected. We conclude from our data that unstimulated respiratory epithelial cells regulate genes associated with NF kappa B dependent immune responses in human macrophages and that these interactions may play a key role in immediate responses in the respiratory mucosa.
