Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of cells, chemotactic factors, and inflammatory mediators are implicated in the complex mechanisms underlying crystal-mediated inflammation. Interleukin-8, released from mononuclear cells that have been exposed to urate and other crystals, is a potent chemotaxin and activator of neutrophils. Experimental and clinical observations suggest that joint movements, local biomechanical factors, and previous joint damage may play a role in influencing the intensity of microcrystalline synovitis and the distribution of articular and periarticular crystal deposits in both calcium pyrophosphate dihydrate crystal deposition disease and gout. There are rare reports of extra-articular calcium pyrophosphate dihydrate crystal deposition in tendons, bursae, dura mater, and ligamentum flavum (with radiculomyelopathy) and of massive "tumoral," tophuslike, periarticular calcium pyrophosphate dihydrate crystal deposits. Synovial fluid levels of ATP, the main substrate for nucleoside triphosphate pyrophosphohydrolase ectoenzyme, which cleaves ATP-releasing inorganic pyrophosphate, are higher in patients with calcium pyrophosphate dihydrate crystal deposition disease than in those with other arthritides, and the levels correlate with inorganic pyrophosphate concentrations. Further reports of acute calcific periarthritis of the first metatarsophalangeal joint (hydroxyapatite pseudopodagra) in young women have been described. The mitogenic response of fibroblasts to stimulation with basic calcium phosphate crystals is accompanied by induction and secretion of collagenase and neutral proteases, implicating a role for the crystals in the pathogenesis of both synovial proliferation and joint damage in chronic basic calcium phosphate crystal-associated arthropathy. Subcutaneous cholesterol crystal deposition with tophus formation is extremely rare and has been described in a patient with scleroderma and calcinosis cutis.
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PMID:Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases. 150 84

Foci of chondrocyte hypertrophy that commonly develop in osteoarthritic (OA) cartilage can promote dysregulated matrix repair and pathologic calcification in OA. The closely related chemokines IL-8/CXCL8 and growth-related oncogene alpha (GROalpha)/CXCL1 and their receptors are up-regulated in OA cartilage chondrocytes. Because these chemokines regulate leukocyte activation through p38 mitogen-activated protein kinase signaling, a pathway implicated in chondrocyte hypertrophic differentiation, we tested whether IL-8 and GROalpha promote chondrocyte hypertrophy. We observed that normal human and bovine primary articular chondrocytes expressed both IL-8Rs (CXCR1, CXCR2). IL-8 and the selective CXCR2 ligand GROalpha (10 ng/ml) induced tissue inhibitor of metalloproteinase-3 expression, markers of hypertrophy (type X collagen and MMP-13 expression, alkaline phosphatase activity), as well as matrix calcification. IL-8 and the selective CXCR2 ligand GROalpha also induced increased transamidation activity of chondrocyte transglutaminases (TGs), enzymes up-regulated in chondrocyte hypertrophy that have the potential to modulate differentiation and calcification. Under these conditions, p38 mitogen-activated protein kinase pathway signaling mediated induction of both type X collagen and TG activity. Studies using mouse knee chondrocytes lacking one of the two known articular chondrocyte-expressed TG isoenzymes (TG2) demonstrated that TG2 was essential for murine GROalpha homologue KC-induced TG activity and critically mediated induction by KC of type X collagen, matrix metalloproteinase-13, alkaline phosphatase, and calcification. In conclusion, IL-8 and GROalpha induce articular chondrocyte hypertrophy and calcification through p38 and TG2. Our results suggest a novel linkage between inflammation and altered differentiation of articular chondrocytes. Furthermore, CXCR2 and TG2 may be sites for intervention in the pathogenesis of OA.
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PMID:IL-8/CXCL8 and growth-related oncogene alpha/CXCL1 induce chondrocyte hypertrophic differentiation. 1453 Mar 67

The aim of the study was to determine factors of risk and progress of aortal valvular calcinosis (AVC) and aortic ostium stenosis (AOS). The subjects were 85 patients with AVC (42--with aortic valvular stenosis (AVS), and 43--without AOS). The study, which included analysis of the lipid and mineral metabolism, and immunological tests, shows that potential factors of AVC are: age (p < 0. 001), osteoporosis (p < 0.03), mitral ring calcification (p = 0.047), dislipidemia (high serum level of total cholesterol, cholesterol of low density lipoproteins, and apoB, atherogenic shift of apoB/apoA-1 ratio, low level of cholesterol of high density lipoproteins (CHDLP)), disbalance between intecellular matrix synthesis and destruction (high concentration of alkaline phosphatase and its bone fraction, and accelerated deoxypyridinoline excretion), inflammation (high concentration of C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6)). The factors of AOS were: age (p < 0.001), smoking (p < 0.001), osteoporosis (p = 0.004), AVC (p < 0.001), mitral ring calcinosis (p = 0.033), dislipidemia (high levels of cholesterol of low density and very low density lipoproteins, low concentrations of CHDLP, and apoA-1), degradation of extracellular matrix, and inflammation (high concentrations of CRP, fibrinogen, IL-6, and IL-8). Thus, atherogenic dislipidemia and mineral dysmetabolism disorder facilitate AVC. The revealed immune status changes imply the role of inflammation in the development and progress of AVS.
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PMID:[Factors facilitating development of degenerative aortic valvular stenosis]. 1607 46

We studied parameters of inflammatory (tumor necrosis factor a, antagonist of interleukin-1 receptor, interleukin-6 , interleukin-8, C-reactive protein) and destructive (matrix metalloproteinases type 3 and 9, tissue inhibitor of metalloproteinase type 1) processes in dynamics of sequential stages of development of atherosclerotic foci in coronary arteries: unchanged intimal tissue --> lipid stain/streak --> stable young plaque --> unstable vulnerable plaque with inclination to ulceration of rupture --> stable plaque with fibrosis/calcinosis, and in various types of unstable plaques in men with coronary atherosclerosis. Characteristic for unstable plaques parameters of inflammatory activity were elevated levels of interleukins (IL) 6 and 8, C-reactive protein (CRP), of destructive activity -- elevated level of metalloproteinases-9. In inflammatory erosive type of unstable plaques (lowered level of antagonist of interleukin-1 receptor and elevated level of CRP) and in lipid type (elevated levels of IL-6, IL-8 and CRP) inflammatory activity was dominating compared with necrotic type in which dominated destructive activity (elevated level of tumor necrosis factor a and lowered level of tissue inhibitor of metalloproteinase type 1).
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PMID:[Activity of inflammatory-destructive changes in the process of formation of unstable atherosclerotic plaque]. 1826 Sep 30