Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04179 (MnSOD)
2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial lipoproteins (LP) are a family of cell wall components found in a wide variety of bacteria. In this study, we characterized the response of HUCL, a telomerase-immortalized human corneal epithelial cell (HCEC) line, to LP isolated from Staphylococcus (S) aureus. S. aureus LP (saLP) prepared by Triton X-114 extraction stimulated the activation of NF-kappaB, JNK, and P38 signaling pathways in HUCL cells. The extracts failed to stimulate NF-kappaB activation in HUCL cells after lipoprotein lipase treatment and in cell lines expressing TLR4 or TLR9, but not TLR2, indicating lipoprotein nature of the extracts. saLP induced the up-regulation of a variety of inflammatory cytokines and chemokines (IL-6, IL-8, ICAM-1), antimicrobial molecules (hBD-2, LL-37, and iNOS), and homeostasis genes (Mn-SOD) at both the mRNA level and protein level. Similar inflammatory response to saLP was also observed in primarily cultured HCECs using the production of IL-6 as readout. Moreover, TLR2 neutralizing antibody blocked the saLP-induced secretion of IL-6, IL-8 and hBD2 in HUCL cells. Our findings suggest that saLP activates TLR2 and triggers innate immune response in the cornea to S. aureus infection via production of proinflammatory cytokines and defense molecules.
...
PMID:Staphylococcus aureus lipoproteins trigger human corneal epithelial innate response through toll-like receptor-2. 1819 35

When monocytes are recruited to inflammation/infection sites, extravasate and differentiate into macrophages, they encounter increasing levels of oxidative stress, both from exogenous and endogenous sources. In this study, we aimed to determine whether there are specific biochemical mechanisms responsible for an increase in oxidative stress resistance in differentiating macrophages. We performed experiments on in vitro cell line models of the monocyte-macrophage differentiation axis (less differentiated THP-1 cells and more differentiated Mono Mac 6 cells). At the same time, we verified the hypothesis that activating monocyte/macrophage innate immune response by pathogens (exemplified by stimulating the TLR2 pattern recognition receptor) would further strengthen cellular antioxidant defences. We found that resistance to exogenous oxidative stress increased substantially both during differentiation and upon activation of TLR2. This increase in antioxidant resistance was accompanied by decrease in free radical damage to cellular proteins. On the molecular level, this resistance was mediated especially by increased levels and activity of glutathione, glutathione-related antioxidant enzymes and Mn superoxide dismutase, as shown by gene expression assays, Western blotting and enzyme activity assays. Moreover, upon TLR2 activation additional molecular mechanisms came into play, conferring additional resistance levels even upon differentiated macrophage-like cells, mainly related to thioredoxin-linked antioxidant enzymes.
...
PMID:TLR2 activation induces antioxidant defence in human monocyte-macrophage cell line models. 2890 38