IL-10 expression profiling in human monocytes.

Lynn Williams; Gabor Jarai; Alexandra Smith; Peter Finan

Home/Archive/PubMed

PubMed · 12377950

IL-10 expression profiling in human monocytes.

Lynn Williams·Gabor Jarai·Alexandra Smith·Peter Finan

View original source ↗Export metadata ↓

Abstract

Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine with numerous immunomodulatory effects, including the inhibition of proinflammatory cytokine production. The mechanisms by which IL-10 exerts these effects still remain largely unknown. As there is evidence that suggests IL-10-mediated cytokine suppression requires the induction of an intermediate gene, we have used gene-chip technology to identify IL-10-inducible genes in human monocytes. We have been able to identify a total of 19 genes that are up-regulated in response to IL-10. Three of these genes had been identified previously: IL-1ra, suppressors of cytokine signaling-3, and CD163; however, the other 16 represent newly identified IL-10-responsive genes. Further analysis of the regulation of eight of these genes showed a remarkable specificity to regulation by lipopolysaccharides (LPS) and IL-10, but not by other anti-inflammatory mediators such as IL-4 and transforming growth factor-beta, suggesting that two diverse stimuli such as IL-10 and LPS may engage common signaling mechanisms.

Explore related subjects

Anti-Inflammatory Agents Cells, Cultured Dexamethasone Down-Regulation Gene Expression Profiling Gene Expression Regulation Humans Interleukin-10 Interleukin-4 Kinetics Lipopolysaccharides Macrophages Monocytes T-Lymphocytes Transforming Growth Factor beta Journal Article

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Lynn Williams, Gabor Jarai, Alexandra Smith, Peter Finan. 2002. IL-10 expression profiling in human monocytes.. https://pubmed.ncbi.nlm.nih.gov/12377950/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2003

Glucocorticoids inhibit induced and non-induced mRNA accumulation of genes encoding hyaluronan synthases (HAS): hydrocortisone inhibits HAS1 activation by blocking the p38 mitogen-activated protein kinase signalling pathway.

OBJECTIVE: Glucocorticoids are still a mainstay in the treatment of rheumatoid arthritis (RA). Unfettered hyaluronan release is a hallmark of RA. The discovery of three genes encoding hyaluronan synthase (HAS) led us to investigate the effect of hydrocortisone and dexamethasone on the activation of these genes at the molecular level and, at least in part, the mode of action of these drugs. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to monitor levels of HAS1, HAS2, and HAS3 mRNAs in cultured fibroblast-like synoviocytes (FS) and in leucocytes isolated from synovial fluid of RA patients. Western blot experiments were used to investigate the effect of hydrocortisone on transforming growth factor beta (TGF-beta)-induced activation of the p38 mitogen-activated protein kinase (MAPK) pathway. RESULTS: Hydrocortisone and dexamethasone suppressed HAS2 and HAS3 mRNAs accumulation concentration-dependently. Contrary to HAS2 and HAS3, HAS1 in FS was not constitutively activated. When cells were stimulated with TGF-beta, a potent activator of HAS1 mRNA transcription, treating them with hydrocortisone suppressed induced activation of HAS1 in a concentration- and time-dependent manner. Similar suppressive effects of hydrocortisone were observed when leucocytes isolated from synovial fluid of inflamed joints were used instead of cultured FS. Furthermore, western blot experiments confirmed that hydrocortisone blocked TGF-beta-induced phosphorylation of p38 MAPK, a kinase essential for TGF-beta-induced HAS activation. CONCLUSION: Our data demonstrate that glucocorticoids suppress all genes encoding hyaluronan. We speculate that inhibition of HAS genes might account for the beneficial effect of glucocorticoid treatment, and also for the detrimental effects of long-term use.

Anti-Inflammatory Agents↗

PubMed2003

Validation of an HPLC method for the determination of ciprofloxacin in human plasma.

A simple HPLC method with fluorescence detection of ciprofloxacin in human plasma was developed and validated. After protein precipitation, chromatographic separation of ciprofloxacin in plasma was achieved at 35 degrees C with a C18 column and acetonitrile-phosphate mixture, pH 3, as mobile phase. Quantitative determination was performed by fluorimetry after excitation at 278 nm. The method was specific and validated with a limit of quantification of 41 ng/ml. The intra- and inter-day coefficients of variation were between 0.5 and 6.6% and accuracy between -2.02 and 7.04%. Ciprofloxacin was stable in plasma for 40 days at -20 degrees C and after three freezing-thawing cycles. The method has been applied in a bioequivalence study of two formulation of 500 mg ciprofloxacin.

Anti-Inflammatory Agents↗

PubMed2003

The dual role of dexamethasone on anti-inflammation and outflow resistance demonstrated in cultured human trabecular meshwork cells.

PURPOSE: Dexamethasone (DEX) is a glucocorticoid commonly used in topical eyedrops to treat eye inflammation. It has an undesirable effect of inducing glaucoma in certain patients. In human Trabecular Meshwork (TM) cells DEX regulates a number of genes but its global influence on TM gene expression is still elusive. In the present work, DEX effects on global gene expressions of an established human TM cell line were studied by microarray. METHODS: The whole experiment of microarray was repeated three times. Differentially expressed genes were identified by an empirical Bayes approach and confirmed by Reverse Transcription Polymerase Chain Reaction. RESULTS: Eight genes (GAS1, CDH4, MT1L, CST3, ATF4, ASNS/TS11, CHOP, HSPA5) were identified that are at least a thousand times more likely to be differentially expressed due to DEX treatment and six genes (TSC22, LDHA, IGFBP2, TAGLN, SCG2, WARS) were identified that are at least a hundred times more likely to be differentially expressed due to DEX treatment. Except for MT1L, ASNS/TS11, IGFBP2, SCG2, and WARS, all the other genes are first reported here to be regulated by DEX in TM. Intriguingly, several of them have overlapping roles in anti-inflammatory response and outflow resistance. CONCLUSIONS: The results of our experiments on cultured human TM cells indicate that the increase in outflow resistance and ultimate ocular hypertension may be byproducts of the favorable anti-inflammatory response triggered by DEX.

Anti-Inflammatory Agents↗