Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblasts, a major constituent of gingival connective tissue, can produce immunoregulatory cytokines and proteolytic enzymes that may contribute to tissue destruction. In this study, we evaluated the production of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), and plasminogen activators by gingival fibroblasts stimulated with lipopolysaccharides (LPS) produced by periodontopathogens, including Actinobacillus actinomycetemcomitans. In addition, changes in the expression and phosphorylation state of fibroblast intracellular signaling proteins induced by A. actinomycetemcomitans LPS were characterized using antibody microarrays. We showed that A. actinomycetemcomitans LPS induced the production of a 50 kDa plasminogen activator, MMP-2 and, to a lesser extent, MMP-3 by fibroblasts. The stimulation of fibroblasts with A. actinomycetemcomitans LPS also resulted in the overproduction of TIMP-1, but had no effect on the production of TIMP-2. Comparable responses were also obtained with Porphyromonas gingivalis and Fusobacterium nucleatum subsp. nucleatum LPS. The results of the microarray analyses showed that A. actinomycetemcomitans LPS induced changes in the phosphorylation state and expression of gingival fibroblast intracellular signaling proteins. More specifically, they suggested that A. actinomycetemcomitans LPS may induce both Jun N-terminus protein-serine kinases (JNK) and mitogen-activated protein-serine kinase p38 alpha (p38alpha MAPK) pathway activation, leading to increased activator protein-1 (AP-1) and nuclear factor kappa-B (NFkappaB) activities, which in turn can stimulate MMP-2, MMP-3, TIMP-1, and urokinase-type plasminogen activator (uPA) expression. This may contribute to periodontal connective tissue destruction.
 ...
PMID:Actinobacillus actinomycetemcomitans lipopolysaccharide regulates matrix metalloproteinase, tissue inhibitors of matrix metalloproteinase, and plasminogen activator production by human gingival fibroblasts: a potential role in connective tissue destruction. 1729 2

Peptostreptococcus micros is a Gram-positive anaerobic bacterium associated with periodontitis, a chronic inflammatory disease affecting tooth-supporting tissues. In the present study, we investigated the response of human macrophages to stimulation with a cell wall preparation from P. micros. In addition, the effect of the preparation on the phosphorylation of macrophage kinases was studied. The preparation, which was non-toxic for macrophages, significantly increased the secretion of the pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6. It also increased the secretion of two potent chemokines IL-8 and, to a lesser extent, RANTES. Lastly, stimulation of macrophages by the P. micros cell wall preparation induced a significant increase in MMP-9 secretion but had no effect on the production of prostaglandin E2. The phosphorylation of macrophage kinases, including cAMP-dependent protein-serine kinase (PKA) catalytic subunit beta, G protein-coupled receptor-serine kinase 2, mitogen-activated protein-serine kinase p38 alpha (p38a MAPK), extracellular regulated protein-serine kinase 2 (ERK2) and Jun N-terminus protein-serine kinases (JNK), increased following stimulation with cell wall. In summary, our study showed that the P. micros cell wall preparation induced intracellular signaling pathways, leading to an increased production of pro-inflammatory cytokines, chemokines and MMP-9 by macrophages.
 ...
PMID:Peptostreptococcus micros cell wall elicits a pro-inflammatory response in human macrophages. 1795 40


<< Previous 1 2