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

A number of inflammatory kidney diseases are associated with interstitial nephritis and influx of leucocytes in the renal interstitium. Potentially the influx of neutrophils in the interstitium may be induced by the chemotactic cytokine IL-8. In the present study we have analysed the production of IL-8 by cultured human proximal tubular epithelial cells (PTEC) in response to a number of proinflammatory cytokines. Primary cell lines of proximal tubular epithelium obtained from ten different kidneys, and cultured under serum-free conditions, were found to produce IL-8 to different degrees from not detectable levels up to 10.8 +/- 1.5 ng IL-8 per 1 x 10(5) cells in 72 h. Gel filtration chromatography of PTEC supernatant indicated that the size of IL-8 of PTEC is 15.1 and 8.1 kD, and is chemotactically active for polymorphonuclear neutrophils (PMN). Addition of 0.5 ng/ml rIL-1 alpha or 1000 U/ml recombinant tumour necrosis factor-alpha (rTNF-alpha) to the culture media of PTEC induced an up-regulation of IL-8 production up to 6.3-fold and 3.0-fold, respectively. The up-regulation by IL-1 alpha and TNF-alpha was dose- and time-dependent. In contrast, 500 U/ml recombinant interferon-gamma (rIFN-gamma) down-regulated the production of IL-8 3.4-fold. Northern blot analysis showed that IL-1 alpha and TNF-alpha increased the expression of IL-8 mRNA, whereas IFN-gamma reduced IL-8 mRNA expression. Taken together, these experiments indicate that human PTEC are a potential source of IL-8 in the kidney, and that IL-8 produced in the proximal tubule can be induced by various proinflammatory cytokines.
 ...
PMID:Regulation and production of IL-8 by human proximal tubular epithelial cells in vitro. 856 14

Beside its role in calcium homeostasis, 1,25-D3 modulates multiple immunological functions in cells of the immune system. In tubular epithelial cells, it increases the expression of HLA-DR and ICAM-1 molecules. Since production of chemokines, such as IL-8 and MCP-1, by tubular epithelial cells is crucial for the inflammatory response in acute transplant rejection and interstitial nephritis, we tested whether 1,25-D3 influences the production of IL-8 and MCP-1 by primary human tubular epithelial cells (TEC). For chemokine detection we used enzyme-linked immunosorbent assays. We differentiated between chemokine secretion directed to the apical and basolateral environment by using cell culture inserts as a model for the tubular basement membrane. mRNA of IL-8 and MCP-1 after stimulation of TEC with IL-1alpha and/or 1,25-D3 was isolated and compared by competitive RT-PCR. We found that basolateral production of IL-8 was higher than luminal secretion. 1,25-D3 (10(-8) M) alone and in combination with IL-1alpha suppressed IL-8 production after 48 h. Basolateral compared to luminal MCP-1 secretion was higher after stimulation either with IL-1alpha alone or combined with 1,25-D3. After 72 h, 1,25-D3 enhanced the IL-1alpha-stimulated MCP-1 secretion. Increased IL-8 mRNA expression after stimulation with IL-1alpha was suppressed by coincubation with 1,25-D3, while MCP-1 mRNA synthesis was enhanced by 1,25-D3 alone and in combination with IL-1 alpha. We conclude that 1,25-D3 differently modulates the expression of CXC-chemokine IL-8 and CC-chemokine MCP-1 by human TEC. The differential effects of 1,25-D3 on renal tubular cytokine secretion have to be considered in therapeutic dials on this hormone, e.g. in renal transplant rejection.
 ...
PMID:1,25-dihydroxyvitamin D3 differentially regulates IL-1alpha-stimulated IL-8 and MCP-1 mRNA expression and chemokine secretion by human primary proximal tubular epithelial cells. 1134 Mar 7

In acute bacterial renal infections, which are most frequently caused by Escherichia coli, tubuloepithelial cells are involved with respect to bacterial adherence, invasion and cytotoxicity. In addition, cytokines expressed by tubuloepithelial cells may be relevant for the recruitment of inflammatory cells and tissue damage in bacterial interstitial nephritis. We asked which inflammatory cytokines are produced by primary human tubuloepithelial cells following in vitro exposure to E. coli and found no release of IL-6, IL-8 and TNF-alpha by tubular cells challenged by bacteria. Purified virulence factors (fimbriae, lipopolysaccharide) from E. coli were also without effects on cytokine release by tubular cells. Since lymphocytic infiltration is a characteristic feature in the chronic form of interstitial nephritis, MHC class II expression by tubular cells in response to bacterial coincubation was analyzed. Exposure to both IFN-gamma and E. coli enhanced MHC class II expression on tubuloepithelial cells. In conclusion, tubuloepithelial cells may play an active role in the local defense against bacteria, e.g. by expressing MHC class II molecules. However, in vitro inflammatory cytokines are not induced by E. coli in this cell population.
 ...
PMID:Absence of cytokine response to bacterial challenge in human tubuloepithelial cells. 1143 42